Methods and devices for endovascular ablation of a splanchnic nerve

ABSTRACT

Systems, devices, and methods for transvascular ablation of target tissue are disclosed herein. The devices and methods may, in some examples, be used for splanchnic nerve ablation to increase splanchnic venous blood capacitance to treat at least one of heart failure and hypertension. For example, the devices disclosed herein may be advanced endovascularly to a target vessel in the region of a thoracic splanchnic nerve (TSN), such as a greater splanchnic nerve (GSN) or a TSN nerve root. Also disclosed are method of treating heart failure, such as HFpEF, by endovascularly ablating a thoracic splanchnic nerve to increase venous capacitance and reduce pulmonary blood pressure.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/963,559, filed Jul. 21, 2020, which is a 371 of internationalApplication No. PCT/US2019/015400, filed Jan. 28, 2019, which claims thebenefit of the following U.S. provisional applications: Application No.62/622,407, filed Jan. 26, 2018, Application No. 62/625,183, filed Feb.1, 2018, and Application No. 62/625,195, filed Feb. 1, 2018, all ofwhich are fully incorporated by reference herein for all purposes.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

This document is related by subject matter to US Pub. No. 2018/0110561,PCT Pub. No. WO2018/023132, and PCT Application No. PCT/US2018/066047(filed Dec. 17, 2018), all of which are incorporated by reference hereinin their entireties for all purposes.

BACKGROUND

Heart failure (HF) is a medical condition that occurs when the heart isunable to pump sufficiently to sustain the organs of the body. Heartfailure is a serious condition and affects millions of patients in theUnited States and around the world.

One common measure of heart health is left ventricular ejection fraction(LVEF) or ejection fraction. By definition, the volume of blood within aventricle immediately before a contraction is known as the end-diastolicvolume (EDV). Likewise, the volume of blood left in a ventricle at theend of contraction is end-systolic volume (ESV). The difference betweenEDV and ESV is stroke volume (SV). SV describes the volume of bloodejected from the right and left ventricles with each heartbeat. Ejectionfraction (EF) is the fraction of the EDV that is ejected with each beat;that is, it is SV divided by EDV. Cardiac output (CO) is defined as thevolume of blood pumped per minute by each ventricle of the heart. CO isequal to SV times the heart rate (HR).

Cardiomyopathy, in which the heart muscle becomes weakened, stretched,or exhibits other structural problems, can be further categorized intosystolic and diastolic dysfunction based on ventricular ejectionfraction.

While a number of drug therapies successfully target systolicdysfunction and HFrEF, for the large group of patients with diastolicdysfunction and HFpEF no promising therapies have yet been identified.The clinical course for patients with both HFrEF and HFpEF issignificant for recurrent presentations of acute decompensated heartfailure (ADHF) with symptoms of dyspnea, decreased exercise capacity,peripheral edema, etc. Recurrent admissions for ADHF utilize a largepart of current health care resources and could continue to generateenormous costs.

While the pathophysiology of HF is becoming increasingly betterunderstood, modern medicine has, thus far, failed to develop newtherapies for chronic management of HF or recurrent ADHF episodes. Overthe past few decades, strategies of ADHF management and prevention haveand continue to focus on the classical paradigm that salt and fluidretention is the cause of intravascular fluid expansion and cardiacdecompensation.

Thus there remains a need for improved therapies for heart failurepatients that are safe and effective, and devices and systems that areadapted and configured to perform those therapies.

SUMMARY OF THE DISCLOSURE

The following first part of the summary is intended to introduce thereader to various aspects of methods for endovascular ablation of one ormore thoracic splanchnic nerves or nerve roots (e.g., greater splanchnicnerves or nerve roots), but not necessarily to define or delimit anyinvention, or limit the disclosure.

The disclosure is related to methods of, devices for, and approaches forablating one or more thoracic splanchnic nerves or thoracic splanchnicnerve roots. The ablations can be performed to treat at least one ofhypertension and heart failure, but the general methods may also be usedfor other treatments as well. For example, the methods herein can beused in the treatment of pain, or even to generally benefit the subjectto reducing the amount of blood that is expelled from the splanchnic bedinto the central thoracic veins.

The treatments herein may be accomplished by increasing splanchniccapacitance. The therapies generally include ablating one or more of apatient's preganglionic thoracic splanchnic nerves or thoracicsplanchnic nerve branches to increase splanchnic capacitance, andthereby treat at least one of hypertension and heart failure.

Methods herein describe ablating thoracic splanchnic nerves, such as agreater splanchnic nerve or greater splanchnic nerve roots. Whilemethods herein may provide specific examples of targeting greatersplanchnic nerve or greater splanchnic nerve roots, it may be possibleto alternatively, or in addition to, ablate other thoracic splanchnicnerves (e.g., lesser, least) to perform one or more treatments herein.

One aspect of the disclosure is a method of ablating tissue bypositioning a medical device intravascularly in the vicinity of targettissue and using the medical device to ablate tissue and create alesion. One aspect of the disclosure is a method of ablating tissue bypositioning a medical device intravascularly into one or more targetvessels and using the medical device to ablate tissue and create alesion. The methods herein can thus be described as methods thatposition a medical device near target tissue to be ablated and/ormethods that position a medical device in one or more vessels, where thetarget tissue is relatively near to the target regions within the one ormore vessels. Any of the method steps herein (including, for examplewithout limitation, in the claims or the Description section) can beincorporated into any other method of use herein unless specificallyindicated to the contrary herein.

One aspect of the disclosure is a method of ablating a greatersplanchnic nerve or a greater splanchnic nerve root to increasesplanchnic venous blood capacitance, the method including advancing amedical device into a first vessel, advancing the medical device into asecond vessel, and delivering ablation energy from the medical device tocreate a lesion in tissue surrounding the first vessel.

In some embodiments the first vessel is an azygous vein and the secondvessel is an intercostal vein.

In some embodiments an intercostal vein is one of the three lowestintercostal veins.

In some embodiments an intercostal vein is a T9, T10, or T11 intercostalvein.

The methods can include positioning a distal end of an ablation elementin the second vessel and no more than 30 mm (e.g., 20 mm, 15 mm, 12 mm)from a junction between the first vessel and the second vessel whendelivering the energy.

The methods can include a proximal portion of an ablation being disposedin the second vessel when delivering energy.

The methods can include delivering fluid from a fluid lumen of themedical device into a membrane, wherein the membrane at least partiallydefines a fluid chamber. Delivering the fluid can inflate the membraneand cause it to change configuration to an expanded configuration orstate. Expanding the membrane may cause the membrane to have an outerdiameter larger than a size of the vessel.

The methods can include positioning the ablation element into contactwith a wall of the second vessel, optionally along the entire length ofthe ablation element, or at least along an active ablation length of theablation element.

The methods can include expanding the membrane so that it has an outerdiameter from 2 mm to 4 mm.

Creating the lesion can include creating a lesion that has a depth of atleast 5 mm around the ablation element.

Creating the lesion can include ablating a portion of a thoracicsplanchnic nerve or a thoracic splanchnic nerve root, e.g., a greatersplanchnic nerve or GSN root.

The lesion may be a continuous lesion. The lesion may have a length from5 mm to 20 mm, such as 10 mm to 20 mm, such as 12 mm to 18 mm.

The lesion may be a circumferential lesion all the way around the secondvessel. The lesion may be less than circumferential all the way aroundthe second vessel, such as 225 degrees or less, 180 degrees or less, 135degrees or less, 90 degrees or less, 45 degrees or less.

The methods can include positioning an entire ablation element in thesecond vessel, while the method can also include positioning less thanthe entire length of the ablation element in the second vessel.

The methods can include performing an ablation process in more than onetarget vessel, such as an intercostal vein or an azygous vein. Themethods of ablation herein can also be performed in the second vessel.

The methods can include performing an ablation confirmation test, suchas any of the tests herein. If desired or needed, an ablation elementmay be repositioned into a second target vessel, which may be an azygousvein or a different intercostal vein.

The methods can create a continuous lesion that has a length from 1 mmto 20 mm, such as from 5 mm to 20 mm, such as from 10 mm to 20 mm.

The methods can also include, prior to, during, and/or subsequent todelivering the ablation energy, delivering stimulation energy to atleast one of first and second stimulation electrodes carried by themedical device. Delivering stimulation energy may help determine if theablation element is in a target location within the intercostal vein,and/or if an ablation procedure was effective.

One aspect of the disclosure is a method of ablating a thoracicsplanchnic nerve or a thoracic splanchnic nerve root to treat at leastone of hypertension and heart failure, comprising: advancing an elongatemedical device into an intercostal vein, the elongate medical devicecomprising an ablation member disposed at a distal region of the medicaldevice; expanding the ablation member within the intercostal vein;activating the ablation member to create an electromagnetic field intissue around the intercostal vein. The method can include heatingtissue surrounding the intercostal vein to a temperature of up to 99degrees C. and ablating a thoracic splanchnic nerve or a thoracicsplanchnic nerve root.

One aspect of the disclosure is a method of transvascular ablation oftarget tissue, the method include delivering an ablation catheterthrough a patient's vasculature to a first vessel, the ablation cathetercomprising at least one energy delivery element; advancing the at leastone energy delivery element into a second vessel, the second vesseldirectly connecting to the first vessel; and delivering ablation energyfrom the at least one energy delivery element to the target tissue. Theablation catheter can include at least one RF electrode that has adiameter that is within 1 mm of the diameter of the second vessel (e.g.,within 1 mm less than or greater than the diameter of the secondvessel).

The energy delivery element can include an RF electrode, microwaveantenna, ultrasound transducer, cryogenic applicator, and/or thermalelement. The step of advancing the at least one energy delivery elementcan include advancing a distal end of the energy delivery element nomore than 30 mm, such as no more than 20 mm, into the second vessel fromthe first vessel. In an embodiment the at least one energy deliveryelement has the same diameter during the step of advancing and the stepof delivering ablation energy. In some embodiments the at least oneenergy delivery element has a greater diameter during the step ofdelivering ablation energy than the advancing step.

Any of the other method steps herein that are described in the contextof other methods can be performed with this exemplary method.

Another aspect of the disclosure is a method of transvascular ablationof a greater splanchnic nerve comprising the following steps: deliveringan ablation catheter comprising a distal region, an ablation element onthe distal region, and two nerve stimulation electrodes positioneddistal and proximal to the ablation element to an intercostal vein;positioning the ablation element in a target region within theintercostal vein; measuring a first physiological condition withoutdelivering energy from the ablation catheter to establish a baselineresponse; delivering a nerve stimulation signal in bipolar mode to thetwo nerve stimulation electrodes; measuring a second physiologicalcondition during the nerve stimulation signal delivery; if the secondphysiological condition shows an increased sympathetic response comparedto the first physiological condition, then delivering ablation energyfrom the ablation element; following or during ablation energy delivery,delivering a second nerve stimulation signal and measuring a thirdphysiological condition; if the third physiological condition shows adecreased sympathetic response compared to the first physiologicalcondition, removing the catheter from the patient; adjusting theposition of the ablation element within the intercostal vein or movingit to a different intercostal vein and repeating the steps betweendelivering the nerve stimulation signal to delivering ablation energy ifthe second physiological condition does not show an increasedsympathetic response compared to the first physiological condition;moving the ablation element to an adjacent intercostal vein andrepeating the steps between delivering the nerve stimulation signal todelivering ablation energy if the third physiological condition does notshow a decreased sympathetic response compared to the firstphysiological condition.

A physiological condition may be, for example, venous compliance and themeasuring may comprise a leg raise test, a hand-grip test, and/or a testthat activates SNS.

Any nerve stimulation signals herein may comprise, for example, 50 Hzand 1 V.

One aspect of the disclosure is a method that includes delivering anablation catheter comprising an energy delivery element (or member)through a venous system of the patient, positioning the energy deliveryelement at least partially (optionally completely) inside a veinselected from T9, T10 and T11 intercostal veins, delivering ablationenergy from the energy delivery element to create a continuous lesionhaving a depth of at least 5 mm and a length from 10 to 20 mm. Thecontinuous lesion and its parameters can be formed by selecting orchoosing certain energy delivery parameters that will create the lesion.In some embodiments, the lesion can extend from an ostium of an azygosvein to up to 20 mm along the intercostal vein.

Any of the other method steps herein that are described in the contextof other methods can be performed with this exemplary method.

In some alternative methods herein, a plurality of ablations (i.e., fromablation energy on to energy ablation off) can be performed within asingle target vessel (e.g., an intercostal vein) to create a totallesion made from two or more lesions made from the plurality ofablations. The total lesion made from the plurality of lesions can haveany of characteristics of the other lesions herein. For example, thetotal lesion can be continuous (made by the connection of a plurality oflesions created during different ablations), can be up to 20 mm long,can be circumferential (or not), etc. After a first ablation, theablation device can be moved within the same vessel and create a secondlesion, which may or may not overlap with a first lesion. This can berepeated as many times as desired. Any of the stimulation or testingsteps herein can be performed before, during, or after any ablationstep, even if a plurality of ablations are performed in a single vessel.

One aspect of the disclosure is an ablation device (e.g., an ablationcatheter) adapted for endovascular ablation of a patient's greatersplanchnic nerve or a greater splanchnic nerve root. The device mayinclude a flexible shaft having a distal section and a proximal section,at least one ablation element carried by the distal section (directly orindirectly), wherein the at least one ablation element has an activeablation length from 1 mm to 20 mm (optionally from 5 mm to 20 mm) andan outer diameter from 2 mm to 4 mm. The active ablation length may befrom 10 mm to 20 mm, e.g., 12 mm to 18 mm.

One aspect of the disclosure is an ablation device for endovascularablation of a patient's greater splanchnic nerve or a greater splanchnicnerve root, including a flexible shaft having a distal section and aproximal section; a fluid lumen extending through at least a portion ofthe flexible shaft; and at least one ablation element disposed at thedistal section, the at least one ablation element comprising a membranewith an active ablation length from 1 mm to 20 mm (e.g., from 5 mm to 20mm) and an outer diameter from 2 mm to 4 mm, the membrane defining aninterior volume in fluid communication with the fluid lumen.

With any of the ablation devices herein, the ablation element can beadapted and configured to create a circumferential lesion around a bloodvessel in which it is placed.

With any of the ablation devices herein, the ablation element can beadapted and configured to create a lesion less than circumferentialaround a blood vessel in which it is placed.

With any of the ablation devices herein, an active ablation length ofthe at least one ablation element can be from 10 mm to 20 mm, such asfrom 12 mm to 18 mm.

With any of the ablation devices herein, a distal section of a flexibleshaft can be adapted and configured to bend at a bend angle of at least90 degrees and with a bend radius of between 4 mm and 15 mm.

With any of the ablation devices herein, the at least one ablationelement can be adapted and configured to have a delivery configurationwith a length from 5 mm to 20 mm and an outer diameter from 1.5 mm to2.5 mm.

With any of the ablation devices herein, the device can further includea proximal stimulation electrode positioned proximal to an ablationelement, and a distal stimulation electrode positioned distal to anablation element, optionally wherein each of the proximal stimulationelectrode and the distal stimulation electrode are no more than 5 mmfrom the ablation element.

With any of the ablation devices herein, the device can further includea proximal stimulation electrode positioned proximal to an ablationelement, and a distal stimulation electrode positioned distal to anablation element, wherein the proximal stimulation electrode and thedistal stimulation electrode can be separated by a distance of no morethan 25 mm.

With any of the ablation devices herein, an active ablation length maybe between 12 and 18 mm.

With any of the ablation devices herein, a distal section of saidflexible shaft may be configured to bend according to a bend angle of atleast 90 degrees and a bend radius of between 4 mm and 15 mm.

With any of the ablation devices herein, the device may further includeat least one temperature sensor, optionally positioned inside anablation element. The at least one ablation element and the at least onetemperature sensor may be connectable to an ablation energy source.

With any of the ablation devices herein, one or more nerve stimulationelectrodes may be 1.5 mm+/−0.5 mm long.

With any of the ablation devices herein, the device may further comprisea temperature sensor exterior to the ablation element, which can includebeing carried by a surface of an ablation element.

With any of the ablation devices herein, an ablation element can beconfigured to emit ablative energy from a segment of the circumferenceof the distal region. For example, the segment may be a percentage ofthe circumference selected from a list of 50%, 40%, 30%, or 25% of thecircumference. The segment can also be described as an angle, such asless than 225 degrees, 180 degrees or less, 135 degrees or less, 90degrees or less, or 45 degrees or less. The remainder of thecircumference not adapted to emit ablative energy may optionallycomprise an electrically resistive material (e.g., disposed on or withina membrane layer). Optionally, the segment can be defined by afenestration in a sheath. The distal region of the device may furthercomprise a radiopaque marker configured to indicate radial orientation.For example, the radiopaque marker may be radially aligned with thesegment adapted to emit ablative energy.

With any of the ablation devices herein, a distal tip may be tapered tofacilitate delivery from a first vessel to a second vessel having asmaller lumen diameter.

With any of the ablation devices herein, the device can further comprisea distal tubular extension having greater flexibility than an elongatetubular shaft, and wherein a guidewire lumen optionally extends throughthe distal tubular extension.

With any of the ablation devices herein, the active ablation length ofthe ablation element is considered the length of the ablation elementthat is in contact with, or configured to be in contact with, tissueduring an ablation step.

The following second part of the summary is intended to introduce thereader to various aspects of devices for endovascular vein puncture, butnot to define or delimit any invention.

According to a 1st aspect of a device for endovascular vein puncture,the device includes an elongate catheter extending along a longitudinalcatheter axis and having a catheter proximal portion and a catheterdistal portion. The device further includes a needle guide having aneedle guide distal end.

In a 2nd aspect according to the 1st aspect the needle guide has a bluntneedle guide distal end.

In a 3rd aspect according to any one of the preceding aspects, theneedle guide is deployable from the catheter from a needle guide storageposition to a needle guide working position. In the needle guide workingposition, the needle guide distal end is radially spaced from thecatheter, and in the needle guide storage position, the needle guidedistal end is withdrawn towards the catheter relative to the needleguide working position.

In a 4th aspect according to any one of the preceding aspects the devicefurther includes a needle having a sharp puncturing end. The needle isdeployable from within the needle guide from a needle storage positionto a puncturing position. In the needle storage position, the puncturingend is shy of the needle guide distal end, and in the puncturingposition, the puncturing end extends proud of the needle guide distalend.

In a 5th aspect according the 3rd aspect in combination with any one ofthe other preceding aspects, the catheter has a catheter outer diameter.In other words, the cross section of the catheter may present an outerperimeter of substantially circular shape having said outer diameter.

In a 6th aspect according to the preceding aspect, in the puncturingposition, the puncturing end is spaced from the needle guide distal endby a needle deployed distance that is less than the catheter outerdiameter.

In a 7th aspect according to the preceding aspect the needle deployeddistance can be less than 2 mm, or less than 1 mm.

In an 8th aspect according to any one of the preceding three aspects, inthe needle guide working position, the needle guide distal end is spacedfrom the catheter in the radial direction by a needle guide deployeddistance that is less than the catheter outer diameter.

In a 9th aspect according to the preceding aspect, the needle guidedeployed distance can be between about 0.5 mm and 6 mm, or between about0.5 mm and about 3 mm, or between about 2 mm and about 6 mm.

In a 10th aspect according to the 3rd aspect in combination with any oneof the other preceding aspects, the catheter has a circumferential outersurface and a first side port in the circumferential outer surface, andthe needle guide is deployable from the first side port.

In an 11th aspect according to the 4th aspect in combination with anyone of the other preceding aspects, the device further includes adelivery device deployable from within the needle from a delivery devicestorage position to a delivery device treatment position.

In a 12th aspect according to the preceding aspect, the delivery devicecan be at least one of a fluid delivery device, a thermal energydelivery device, a radiofrequency energy delivery device, a cryogenicenergy delivery device, and an electrical energy delivery device.

In a 13th aspect according to any one of the preceding two aspects, thedelivery device can have a blunt delivery device distal end.

In a 14th aspect according to any one of the preceding three aspects, inthe delivery device treatment position, the delivery device distal endcan extend proud of the puncturing end by a delivery distance that isgreater than the puncturing distance.

In a 15th aspect according to the preceding aspect, the deliverydistance can be up to 15 mm, or between about 3 mm and about 7 mm, orbetween about 4 mm and about 6 mm.

In a 16th aspect according to any one of the preceding aspects, thecatheter includes a guidewire lumen extending therethrough, along thecatheter axis, and the catheter distal portion has a guidewire exitport.

In a 17th aspect according to the preceding aspect, the catheterincludes a distal end surface and a circumferential outer surface, andthe guidewire exit port is a notch that is open at and between thedistal end surface and the circumferential surface.

In a 18th aspect according to the 3rd and the 17th aspects, the needleguide is deployable from the catheter at a first circumferentialposition on the catheter, and the notch is open at the circumferentialsurface at a notch circumferential position that is within 30 degrees ofthe first circumferential position. Optionally, the notchcircumferential position can be aligned with the first circumferentialposition.

In a 19th aspect according to any one of the preceding aspects from the3rd to the 18th, the device further includes a second needle guidedeployable from the catheter, and a second needle deployable from withinthe second needle guide.

In a 20th aspect according to the preceding aspect, the needle guide isdeployable from the catheter at a first longitudinal position on thecatheter, and the second needle guide is deployable from the catheter ata second longitudinal position on the catheter.

In a 21st aspect according to the preceding aspect, the secondlongitudinal position is spaced from the first longitudinal position.

In a 22nd aspect according to any one of the preceding three aspects,the needle guide is deployable from the catheter at a firstcircumferential position on the catheter, and the second needle guide isdeployable from the catheter at a second circumferential position on thecatheter. Optionally, the second circumferential position can be alignedwith the first circumferential position.

In 23rd aspect according to any one of the preceding aspects, the deviceincludes at least a first radiopaque marker. The first radiopaque markercan be on the catheter, the needle guide, or the needle.

In a 24th aspect according to the preceding aspect, the first radiopaquemarker is on the catheter and is configured to indicate a rotationalorientation of the catheter.

In a 25th aspect according to any one of the preceding two aspects, thefirst radiopaque marker is made from a radiopaque material.

In a 26th aspect according to any one of the preceding three aspects,the first radiopaque marker is asymmetric in shape, optionally the firstradiopaque marker is N-shaped.

In a 27th aspect according to any one of the preceding four aspects, thedevice further includes an additional radiopaque marker on the catheterand configured to visually indicate when the rotational position of thecatheter is within a set tolerance.

In a 28th aspect according to the preceding aspect, the additionalradiopaque marker includes two lines the center of which iscircumferentially spaced from the first radiopaque marker by about 180degrees, so that the first radiopaque marker appears between the linesof the additional radiopaque marker when the orientation is within theset tolerance.

In a 29th aspect according to any one of aspects from the 3rd to the28th, in the needle guide working position, the needle guide is eitherstraight or curved and is inclined with respect to the catheter axis.

In a 30th aspect according to any one of the preceding aspects from the3rd to the 29th, the device comprises a controller configured for:

-   -   causing deployment of the needle guide from the needle guide        storage position to the needle guide working position;    -   causing deployment of the needle from the needle storage        position to a puncturing position.

In a 31st aspect according to the preceding aspect, in combination withany one of aspects from the 11th to the 15th, wherein the controller isfurther configured to cause deployment of the delivery device from thedelivery device storage position to the delivery device treatmentposition.

In a 32nd aspect according to any one of the preceding two aspects, thecontroller is an analog or a digital circuit or a combination thereof;the controller is connected to appropriate actuators (such as electricmotors, pneumatic or hydraulic actuators or other type of actuators ormotors) configured to cause deployment of the above mentioned deployablecomponents upon command from the controller.

In a 33rd aspect according to any one of aspects from the 11th to the15th, the delivery device is a cryogenic energy delivery deviceincluding a first lumen for delivery of a cryogenic fluid from a sourceto the distal end of the cryogenic energy delivery device, and a secondlumen for return of the cryogenic fluid to the source.

In a 34th aspect according to the preceding aspect, the source ofcryogenic fluid includes a fluid reservoir, a supply valve between thefluid reservoir and the first lumen, a pressure release valve at theexit of the second lumen for venting the returned cryogenic fluid toatmosphere, and a controller or said controller configured forcontrolling the supply valve and the pressure release valve.

In a 35th aspect according to the preceding aspect, the or a controlleris in communication with a temperature sensor at the distal end of thedelivery device and is configured to control supply of the cryogenicfluid in response to temperature sensed by the temperature sensor.

In a 36th aspect according to any one of the preceding aspects, thedevice is used to ablate a thoracic splanchnic nerve, a thoracicsplanchnic nerve root, or a greater splanchnic nerve.

The following third part of the summary is intended to introduce thereader to various aspects relating methods of endovascular veinpuncture, but not to define or delimit any invention. Optionally themethods described in this third part of the summary may use the devicesaccording to any one of the preceding aspects.

According to some aspects, a method for endovascular puncture andtreatment includes a. advancing a catheter distal portion through avenous system of a patient to a target location within a vein; b.deploying a needle guide from the catheter in a direction that istransverse to a longitudinal axis of the catheter; c. contacting a veinwall with a blunt distal end of the needle guide and continuing todeploy the needle guide to force the blunt distal end against the veinwall; d. deploying a needle from the distal end of the needle guide topuncture the vein wall with a sharp puncturing end of the needle; and e.delivering a treatment to a region exterior to the vein via the sharppuncturing end.

In some examples, the catheter has a catheter outer diameter, and stepb. includes deploying the needle guide to a deployed distance that isless than the catheter outer diameter. The deployed distance can bebetween 0.5 mm and 6 mm, or between 0.5 mm and 3 mm, or between 2 mm and6 mm.

In some examples, the catheter has a catheter outer diameter, and stepd. includes deploying the needle to a puncturing distance that is lessthan the catheter outer diameter. The puncturing distance can be lessthan 2 mm, or less than 1 mm.

In some examples the method includes, prior to step e., delivering anerve stimulation test pulse via the blunt distal end or the sharppuncturing end.

In some examples step e. includes deploying a delivery device from thepuncturing end and using the delivery device to deliver the treatment.Step e. can include deploying the delivery device by a delivery distancethat is greater than the puncturing distance. The delivery distance canbe up to 15 mm, or between 3 mm and 7 mm, or between 4 mm and 6 mm.

In some examples, step e. includes ablating a nerve.

In some examples, step e. includes delivering at least one of a fluid, athermal energy treatment, a cryogenic energy treatment, and aradiofrequency energy treatment.

In some examples, the target location is within an azygos vein or anintercostal vein. The target location can be within a T9, T10, or T11intercostal vein. The target location can be within an azygos veinbetween a T11 and T9 intercostal vein.

In some examples, step e. includes delivering a treatment to a thoracicsplanchnic nerve or a thoracic splanchnic nerve root.

In some examples, step e. includes delivering a treatment to a greatersplanchnic nerve.

In some examples, step e. includes delivering a treatment for heartfailure.

In some examples, the method includes co-ordinating step e. with thepatient's breathing to avoid damaging a lung of the patient with thetreatment. The method can include monitoring a proximity of the needleto the patient's lung.

In some examples, step a. includes advancing the catheter over aguidewire. The target location can be in an azygos vein, and theguidewire can extend beyond the azygos vein into an intercostal vein.The method can include, prior to step b., orienting the catheter at atarget orientation by rotating the catheter until the guidewire ispositioned in an orienting notch of the catheter distal portion. Step b.can include deploying the needle guide from a side port in acircumferential outer surface of the catheter. The notch can be at anotch circumferential position, and the side port can be at a firstcircumferential position that is within 30 degrees, or within 20degrees, or within 10 degrees of the notch circumferential position.

In some examples, the method includes, after step a., deploying a secondneedle guide from the catheter in a second direction transverse to thelongitudinal axis of the catheter, contacting the vein wall with asecond blunt distal end of the second needle guide and continuing todeploy the second needle guide force the second blunt distal end againstthe vein wall, deploying a second needle from the second distal end ofthe second needle guide to puncture the vein wall with a secondpuncturing end of the second needle, and delivering a second treatmentvia the second puncturing end. The needle guide can be deployed from afirst side port in the catheter distal portion, the second needle guidecan be deployed from a second side port in the catheter distal portion,and the first side port and second side port can be longitudinallyspaced apart. The first side port and second side port can belongitudinally spaced apart by between 3 cm and 5 cm. The first sideport and second side port can be circumferentially aligned.

In some examples, step c. includes continuing to deploy the needle guideto force the catheter away from the vein wall and abut an opposing veinwall.

One aspect of the disclosure is an ablation method that includesintravascularly puncturing at least one of an intercostal vein and anazygous vein with a medical ablation device; and ablating a thoracicsplanchnic nerve or a thoracic splanchnic nerve root using the medicalablation device. The medical device can be any of the medical devicesdescribed herein.

One aspect of the disclosure is an intravascular medical deviceconfigured to be intravascularly advanced into at least one of anazygous vein and an intercostal vein, the medical device including apuncturing element adapted to be deployed from an outer shaft of theintravascular medical device to puncture at least one of the azygousvein and an intercostal vein, such as any of the relevant medicaldevices herein.

The following fourth part of the summary is intended to introduce thereader to various aspects relating transvascular nerve ablationembodiments, but not to define or delimit any invention. Optionally themethods described in this fourth part of the summary may use the devicesaccording to any one of the preceding or following aspects.

One aspect is an ablation catheter configured for intravascular nerveablation, in particular for intravascular splanchnic nerve ablation,comprising: an elongated shaft, an ablation assembly carried by aportion of the elongated shaft, wherein the ablation assembly isconfigured to form either a circumferential ablation pattern having atleast, for example, 12 mm length or a directional ablation patternhaving at least, for example, 12 mm length.

The ablation assembly may be configured to form either a circumferentialablation pattern having a length between 12 and 30 mm, optionallybetween 12 and 20 mm, or a directional ablation pattern having a lengthbetween 12 and 30 mm, optionally between 12 to 20 mm.

The ablation assembly may be carried by a distal straight portion of theelongated shaft.

The ablation assembly may further comprise an expandable member carriedby the elongate shaft and having an unexpanded state and an expandedstate, wherein the ablation assembly is mounted to the expandablemember.

The catheter can be configured for insertion in a human arterial vein.

The expandable member, in the unexpanded state, can be configured forinsertion in an intercostal vein of a human patient and, in the expandedstate, can be configured for abutting against a vessel wall of saidintercostal vein.

The expandable member, in the expanded state, can comprises acircumferential treatment zone configured to contact a vessel wall andhave a length in a range of 12 to 30 mm, optionally of 12 to 20 mm,extending along a longitudinal axis of the catheter, the circumferentialtreatment zone.

The expandable member can have, in the unexpanded state, a diameter in arange of about 1 mm to 2.5 mm and a circumference in a range of about3.14 mm to 7.85 mm.

The expandable member can have, in the expanded state, a diameter in arange of about 3 mm to 5 mm and a circumference in a range of about 9.4mm to 15.7 mm.

The ablation assembly and the expandable member can be configured suchthat, with the expandable member in the expanded state, the ablationassembly forms a circumferential ablation pattern of at least 12 mmlength, preferably of a length between 12 and 30 mm.

The expandable member can comprise a deployable balloon attached to thedistal portion of the elongated shaft and optionally made of compliantmaterial or non-compliant material that flexibly folds to contract.

The elongated shaft can comprise a flexible neck located within 10 mmproximal to the expandable member or within 10 mm proximal to theablation assembly. The flexible neck can be capable of bending accordingto a minimum curvature radius of 4 mm to allow orientation of a distalportion of the elongated shaft and facilitate insertion of the same inan intercostal vein's natural orientation. The flexible neck can be madeof a softer durometer polymer, optionally Pebax, compared to thematerial used for the portion of the elongated shaft proximal to theflexible neck. A wire coil can be embedded in the material of theflexible neck.

The ablation assembly can comprise a plurality of electrode padassemblies mounted on an external surface of the expandable member andconfigured, when the catheter is inserted in a patient's blood vessel,to come into direct contact with a blood vessel wall. Each electrode padassembly can include a plurality of electrodes in the form of electrodepads, the electrode pads being electrically interconnected by anelectrical trace, optionally wherein the electrode pads and the tracesof a same electrode pad assembly are formed by a common electricallyconductive supporting substrate. The electrode pads and electricaltraces of a same electrode pad assembly can be aligned substantiallyparallel to the longitudinal axis of the catheter. The electrode padassemblies can be mounted to the expandable member defining a pluralityof electrode pads positioned around the expandable member forming acircumferential ablation pattern that is up to 20 mm long, optionallywherein the circumferential ablation pattern has a length comprisedbetween 12 and 18 mm. Each electrode pad can be circumferentiallyseparated by a distance of less than 5 mm, optionally less than 2.5 mm,from an angularly adjacent electrode pad. Each electrode pad can extendaround the expandable member along an arc length in a range of 3 mm to3.5 mm. Each electrode pad can have a length, measured parallel to thecatheter longitudinal axis, of about 3 to 5 mm. Each electrode padassembly can develop substantially rectilinearly along the catheter andcomprises a row of electrical pads separated by respective electricaltraces.

The catheter can include a plurality of electrode pad assemblies, eacharranged with multiple electrode pads, the plurality of electrode padassemblies forming rows of electrode pads, optionally at least four rowsof electrode pads connected together by electrical traces. The rows ofelectrode pads can be evenly spaced around the circumference of theexpandable member. The electrode pads on one row can be longitudinallyoffset from the electrode pads of adjacent rows. A space betweenadjacent electrode pads when the expandable member in its unexpandedstate can be smaller than the space between adjacent electrode pads whenthe expandable member in its expanded state. Each electrode pad, whenthe expandable member is expanded, can be circumferentially separatedfrom an adjacent electrode pad by a distance comprised between 0 and 1mm. Adjacent rows of electrode pads can interlock with one another whenthe expandable member in its unexpanded state. When the expandablemember is in its expanded state, each electrode pad can becircumferentially separated from an adjacent electrode pad by a distancecomprised between about 2 mm and 5 mm.

Electrical traces that connect two consecutive electrode pads cancomprise a narrow electrically conductive strip presenting width,measured circumferentially around the expandable member, significantlysmaller than the arc length of the electrode pads, optionally whereinthe width of each electrical trace is smaller than 0.5 mm.

Electrode pad assemblies can be configured to position electrode padsonly on one side of the expandable member, optionally covering between25% and 50% of the expandable member circumference, to generate adirectional ablation pattern that is all toward the same side and of alength of a target ablation zone.

The ablation assembly can comprise a plurality of electrodes in the formof axially spaced tubular electrodes mounted on the elongated shaft.Tubular electrodes can have an external diameter in the range of 2 to 3mm. Tubular electrodes can be consecutively mounted on the elongatedshaft and have spacing between two consecutive tubular electrodes in therange of 2 to 4 mm. Each of the tubular electrodes can have a length inthe 1 to 4 mm range. The catheter can include a plurality of tubularelectrodes positioned along a straight section of the elongated shaft. Aplurality of tubular electrodes can be positioned along a straightsection of the elongated shaft and can span a distance of comprisedbetween 12 and 20 mm. The elongated shaft can have a loop shaped sectionthat is proximal to the straight section. The loop shaped section cancomprise a plurality of tubular electrodes. The tubular electrodes orsections of shaft between the tubular electrodes can include irrigationports configured for delivering fluid and connectable to a fluid source.

The ablation assembly can comprise at least one straight electrodeparallel to the axis of the expandable member having length in a rangeof 12 to 20 mm. The straight electrode can cover a segment of at least25% of the expandable member circumference. The catheter can comprise aplurality of straight electrodes positioned around the expandable memberfor circumferential ablation. The catheter may include exclusively onesingle straight electrode that covers a segment in the range between 25%and 50% of the expandable member circumference for directional ablation.Each straight electrode can be in the form of an electrode strip. Eachstraight electrode can contain one or more irrigation ports configuredto be connected to a source of fluid.

The catheter can comprise a plurality of ultrasound transducerspositioned inside the expandable member. Ultrasound transducers can becarried by a support shaft centered in the expandable member.Transducers can be placed serially spanning a length that is in a rangeof 12 to 20 mm to generate an ablation of a similar length. Struts orprotrusions can be positioned between the transducers and the expandablemember. Struts can comprise polymer strands elastically pre-shaped toradially expand away from the transducers. The transducers, optionallyat least 4 mm long, are spaced apart with flexible gaps between them.The ultrasound transducers can be cylindrical for producingcircumferential ablation around a target vessel. The ultrasoundtransducers can be flat or hemicylindrical to produce an ablation thatis a partial segment of the circumference of a target vessel.

The ablation assembly can comprise a plurality of electrodes and whereinthe expandable member can comprise a basket of elastic struts,optionally including 3 or more rows of struts, each strut having atleast one electrode mounted to it. The basket can have a contracteddelivery state with a diameter of below 2.00 mm, optionally of about 1.7mm. The basket can have an expanded ablation state having a diameter ina range of about 2.5 mm to 4 mm. The catheter can comprise anon-occluding, radially expandable, tubular membrane associated to thestruts, with the electrodes on the outer surface of the tubularmembrane. The tubular membrane can be an electrically insulatingmaterial. The tubular membrane can be connected to, and optionallypositioned over, the struts. The catheter can also include a coolantdelivery port configured for injecting a coolant in a volume externallydelimited by the tubular membrane to allow cooling of the electrodeswith convection. The coolant delivery port can be at the distal end ofthe basket. The struts can comprise narrowed sections between mountedelectrodes that have greater flexibility than the rest of the struts tofacilitate bending. The basket and position of the electrodes can beconfigured to form an ablation pattern that is in a range of 12 to 20 mmlong, optionally 15 mm long. The basket and position of the electrodescan be configured to generate to create a circumferential ablationpattern substantially along the full length of basket. The electrodescan be mounted only on one or two struts of the basket to ablate only acircumferential segment of the vessel for directional ablation. Thecatheter can also include a radiopaque marker that identifies a radialdirection of the basket positioned on the catheter's distal region,optionally on the struts. Each of the struts can have a cross sectionwith a respective maximum width and maximum thickness and wherein eachof the electrodes has a cross section with a respective maximum widthand maximum thickness, wherein the maximum thickness of the electrodesis bigger than the maximum thickness of the struts and wherein themaximum with of the electrodes is bigger than the maximum width of thestruts. Each of the struts can have a cross section with a width ofabout 0.5 mm and thickness of about 0.13 mm. Each of the electrodes canhave a cross section with a width of about 1 mm and a maximum thicknessof about 0.33 mm tapered to narrower thickness at the edges of about0.25 mm.

A power source can be connected to the ablation assembly, and a controlunit can control the power source and be configured to command the powersource to deliver ablation energy, in particular RF ablation energy, tothe ablation assembly. The control unit can be configured to control thepower source such that a larger amount of ablation power, optionally RFenergy, is delivered to proximal electrode(s) than the rest of theelectrode(s) to compensate for the blood flow cooling. The control unitcan be configured to control the power source such that a longerduration of ablation power, optionally RF energy, is delivered toproximal electrode(s) than to the rest of the electrode(s) to compensatefor the blood flow cooling. The control unit can be configured tocontrol the power source to deliver RF ablation energy in at least oneof unipolar mode sequentially, unipolar mode simultaneously, and bipolarmode. The control unit can be configured to control the power source todeliver RF ablation energy with a pulsing waveform. The control unit canbe configured to control the power source and drive bipolar energy, inparticular bipolar RF ablation energy, between pair of electrodes, inparticular between pair of electrode pads of different electrode padassemblies. A coolant source can be connected or connectable to acoolant injection port of the catheter, which can be in fluidcommunication with an inside of the expandable member. A control unitcan also control the coolant source and can be configured to command thecoolant source to inject coolant fluid through said coolant injectionport into the expandable member. The catheter can also include a coolantexit port that is either connected to an exit lumen extending within thecatheter elongated shaft or directly communicating with the outside ofthe catheter such that coolant may be deposited into blood stream. Acoolant exit port can be smaller than the coolant injection port toallow pressure to increase in the expandable member to inflate it.

The catheter can also include a radiopaque marker positioned on a distalregion of the catheter to indicate radial direction, optionally aradiopaque marker is asymmetric and positioned on the same side oropposing side as the electrodes.

The catheter can also include one or more temperature sensors, eachdisposed between pairs of electrodes. A temperature sensor can beconfigured to directly contact a blood vessel wall when the catheter isinserted in a blood vessel and the expandable member is in its expandedstate. A control unit can be configured to receive a temperature signalfrom the temperature sensor and control the coolant source to injectcoolant fluid based on said temperature signal and/or control the powersource emission of ablation energy based on said temperature signal.

The following fifth part of the summary is intended to introduce thereader to various aspects relating dual electrode transvascular nerveablation embodiments, but not to define or delimit any invention.Optionally the methods and devices described in this fifth part of thesummary may use the devices or methods according to any one of thepreceding aspects.

One aspect of this part is a transvascular ablation device adapted andconfigured for transvascular ablation of a preganglionic TSN or TSNnerve root, comprising: a proximal portion adapted to remain outside ofa patient and a distal portion sized for insertion through the patient'svasculature, the distal portion comprising an elongate shaft, a firstablation member carried by the elongate shaft, a second ablation membercarried by the elongate shaft, and an occlusion member carried by theelongate shaft and axially in between the first and second ablationmembers, the occlusion member adapted to have a delivery configurationand an expanded configuration.

The second ablation member may be axially spaced from the first ablationmember by a distance of 3 mm to 6 mm.

At least one of the first ablation member and the second ablation membercan have a length from 3 mm to 5 mm.

An outer diameter of the first ablation member can be from 1.5 mm to 3mm, and an outer diameter of the second ablation member can be from 1.5mm to 3 mm.

The occlusion member can have an axial length of 1 mm to 6 mm.

A diameter of the occlusion member in the expanded configuration can befrom 3 mm to 5 mm, and optionally has a diameter in the deliveryconfiguration from 1.5 mm to 2 mm.

The device can further comprise a guidewire lumen extending from theproximal portion to a guidewire exit port in the distal portion.

The first ablation member can be in electrical communication with afirst electrical conductor, and the second ablation member can be inelectrical communication with a second electrical conductor that isdifferent than the first electrical conductor.

The first and second ablation members can each comprise an irrigationexit port in fluid communication with at least one irrigation lumenpassing though the elongate shaft to the proximal portion where it isconnectable to an irrigation fluid supply.

The first and second ablation members can each comprise an irrigationexit ports in fluid communication with an independent irrigation lumenpassing though the elongate shaft to the proximal portion where they areconnectable to an irrigation fluid supply.

Any irrigation exit port may have a diameter of 0.020″+/−0.005″. Any ofthe irrigation exit ports can be positioned on a side of the first orsecond ablation members, respectively.

The first ablation member can comprise an electrode, the electrodecomprising at least one irrigation exit port positioned in at least onechannel that spans the length of the electrode. The first ablationmember can comprise an electrode, the electrode comprising at least oneirrigation exit port positioned in at least one scallop that spans aportion of a length of the electrode to at least a distal or proximalend of the electrode.

At least one of the first and second ablation members can comprise acavity in fluid communication with at least two irrigation lumenspassing though the elongate shaft to the proximal portion where a firstof the at least two irrigation lumens can be connectable to anirrigation fluid supply and a second of the at least two irrigationlumens can be connectable to a fluid return receiver.

At least one of the first and second ablation members can comprise atemperature sensor.

The occlusion member can be an inflatable occlusion balloon.

The occlusion balloon can comprise a chamber, and the chamber can be influid communication with an inflation lumen passing through the elongateshaft to the proximal portion where it is connectable to an inflationfluid supply. A temperature sensor can be positioned within the chamber,and the temperature sensor can be adapted to monitor a temperature offluid within the chamber.

One aspect of this part is a transvascular ablation device adapted andconfigured for transvascular ablation of a preganglionic greatersplanchnic nerve or nerve root, comprising: a proximal portion adaptedto remain outside of a patient and a distal portion sized for insertionthrough the patient's vasculature, the distal portion comprising anelongate shaft, a first ablation member carried by the elongate shaft, asecond ablation member carried by the elongate shaft and axially spacedfrom the first ablation member, and an occlusion member carried by theelongate shaft and axially in between the first and second ablationmembers, the occlusion member adapted to have a delivery configurationand an expanded configuration.

At least one of the first and second ablation members can have an outerdiameter from 1.5 mm to 3 mm. The occlusion member may have a diameterin the expanded configuration from 3 mm to 5 mm.

At least one of the first and second ablation members can have a lengthfrom 3 mm to 5 mm.

One aspect of this part is a transvascular ablation device adapted andconfigured for transvascular ablation of a preganglionic greatersplanchnic nerve or nerve root, comprising: a proximal portion adaptedto remain outside of a patient and a distal portion sized for insertionthrough the patient's vasculature, the distal portion comprising anelongate shaft, a first ablation member carried by the elongate shaft, asecond ablation member carried by the elongate shaft and axially spacedfrom the first ablation member, wherein the first and second ablationmembers both have outer dimensions, optionally diameters, that are lessthan a diameter of the elongate shaft.

The outer dimensions can be from 1.5 mm to 2.5 mm.

The diameter of the elongate shaft can be from 2 mm to 3 mm.

The outer dimensions can be less than the diameter by 0.2 mm to 1 mm.

A portion of each of the first ablation member and the second ablationmember can be electrically insulated and a remaining portion of each iselectrically conductive, wherein the electrically conductive portioncomprises a segment that is less than or equal to 50% of thecircumference, less than 40%, less than 30%, or less than 25%.

The device can be adapted to be connected to an ablation console, theablation console adapted to operate the ablation device in at least oneof bipolar mode, monopolar mode, and a combination of bipolar andmonopolar modes.

One aspect of this part is a method of ablating a TSN or TSN nerve root(e.g., a greater splanchnic nerve or a greater splanchnic nerve root) toincrease splanchnic venous blood capacitance, comprising: advancing anelongate medical device into an azygous vein, the elongate medicaldevice including a distal region, the distal region including a flexibleshaft, a first ablation member carried by the shaft, and a secondablation member carried by the shaft that is axially spaced from thefirst ablation member, advancing the first ablation member from theazygous vein into a T9, T10, or T11 intercostal vein; deliveringablation energy from the first ablation member; and creating an ablationlesion and thereby ablating a portion of a great splanchnic nerve or agreater splanchnic nerve root.

The method can further comprise advancing the second ablation memberfrom the azygous vein into the T9, T10, or T11 intercostal vein, anddelivering ablation energy from the second ablation member.

The delivering steps can comprise delivering energy from the first andsecond ablation members in monopolar modes.

The delivering steps can comprise delivering energy from the first andsecond ablation members in a bipolar mode.

The delivering steps can comprise delivering energy from the first andsecond ablation members in a combination monopolar-bipolar mode.

The method can also include advancing an occlusion member into the T9,T10, or T11 intercostal vein in between the first and second ablationmembers. The occlusion member can be carried by the elongate shaft inbetween the first and second ablation members. The method can furthercomprise expanding the occluding member in the T9, T10, or T11intercostal vein. The method can further comprise completely occludingthe T9, T10, or T11 intercostal vein with the occlusion member.

Advancing the second ablation member can comprise positioning a proximalend of the second ablation member at an ostium of the azygous vein andthe intercostal vein.

Advancing a first ablation member from the azygous vein into a T9, T10,or T11 intercostal vein can comprise advancing the first ablation memberinto the T9, T10, or T11 intercostal vein up to 20 mm from an ostium ofthe azygous to the intercostal vein, and wherein delivering ablationenergy from the first ablation member can occur when the first ablationmember is positioned up to 20 mm from the ostium.

When energy is delivered from the first ablation member, the secondablation member can be positioned in the azygous vein.

The method can further comprise expanding an occluding member at anostium of the azygous vein and the intercostal vein, and whereinexpanding the occluding member directs blood flow away from the ostium.

Energy can be delivered from the first ablation member in monopolarmode.

Creating the lesion may not include delivering ablation energy from thesecond ablation member.

The first and second ablation members can be operated in bipolar modewhen the second ablation member is positioned in the azygous vein.

Creating an ablation lesion can comprise creating an ablation regionthat has a depth of at least 5 mm from the intercostal vein.

Creating an ablation lesion can comprise creating a circumferentialablation region.

The method can further comprise advancing the first ablation member fromthe azygous vein into one of the other of the T9, T10, and T11intercostal veins and delivering ablation energy from the first ablationmember when in the other of the T9, T10, and T11 intercostal veins.

Creating the lesion may not include delivering ablation energy from thesecond ablation member.

The method can further comprise delivering a stimulation signal from atleast one of the first and second ablation members. Delivering astimulation signal can comprise delivering a stimulation signal betweenthe first and second ablation members in bipolar mode. The method canfurther comprise measuring a response to a stimulation signal.Delivering a stimulation signal and measuring a response can occurbefore delivering ablation energy from the first ablation member.Delivering a stimulation signal and measuring a response can occur afterdelivering ablation energy from the first ablation member.

The method can further comprise advancing an occlusion member into theT9, T10, or T11 intercostal vein proximal to the first ablation member.The occlusion member can be carried by the elongate shaft. The methodcan further comprise expanding the occluding member in the T9, T10, orT11 intercostal vein. The method can further comprise completelyoccluding the T9, T10, or T11 intercostal vein with the occlusionmember. Expanding the occluding member can comprise delivering fluidinto the occluding member.

The method can further comprise delivering irrigation fluid to at leastone of the first and second ablation members. The method can includemonitoring for irrigation fluid that is above a threshold temperature.The method can further comprise altering an energy delivery parameter ifa monitoring step indicates irrigation fluid is above the thresholdtemperature. The method can further comprise controlling an irrigationfluid flow rate.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings included herewith are for illustrating various examples ofarticles, methods, and apparatuses of the present specification and arenot intended to limit the scope of what is taught in any way. In thedrawings:

FIG. 1 is a perspective view of an example device for endovascular veinpuncture.

FIG. 2 is an enlarged perspective view of the distal portion of thecatheter of the device of FIG. 1 .

FIG. 3 is an enlarged perspective view of the distal portion of thecatheter of the device of FIG. 1 , showing a needle guide in a workingposition.

FIG. 4 is an enlarged perspective view of the distal portion of thecatheter of the device of FIG. 1 , showing a needle in a puncturingposition.

FIG. 5 is an enlarged perspective view of the distal portion of thecatheter of the device of FIG. 1 , showing a delivery device in atreatment position.

FIG. 6 is an enlarged perspective view of a distal portion of a catheterof another example device for endovascular vein puncture.

FIG. 7 is a further enlarged perspective view of the distal portion of acatheter of FIG. 6 .

FIG. 8 is an enlarged plan view of the distal portion of the catheter ofFIG. 6 .

FIG. 9 is a schematic view of a portion of the thorax of a patient, witha guidewire in position in a T10 intercostal vein of the patient, andwith the device of FIG. 1 advanced over the guidewire to a targetlocation.

FIG. 10 is the schematic view of FIG. 9 , with the needle guide of thedevice being advanced towards a working position.

FIG. 11 is the schematic view of FIG. 10 , with the needle guide of thedevice in the working position.

FIG. 12 is the schematic view of FIG. 11 , with the needle of the devicebeing in the puncturing position.

FIG. 13 is the schematic view of FIG. 12 , with the delivery device ofthe device in the treatment position proximate a greater splanchnicnerve.

FIG. 14 is a schematic view of a portion of the thorax of a patient,with a guidewire in position in a T11 intercostal vein of the patient,and with the device of FIG. 1 advanced over the guidewire to a targetlocation within the azygos vein.

FIG. 15 is the schematic view of FIG. 14 , with the catheter of thedevice rotated to adjust its orientation, until the guidewire falls intothe notch of the catheter.

FIG. 16 is the schematic view of FIG. 15 , with the needle guides andthe needles deployed.

FIG. 17 is an enlarged top plan view of the distal portion of thecatheter of an alternative example device for endovascular veinpuncture.

FIG. 18 is a schematic view showing the appearance of the radiopaquemarker of the device of FIG. 17 under fluoroscopy, when the device is ata desired rotational orientation.

FIG. 19 is a schematic view showing the appearance of the radiopaquemarker of the device of FIG. 17 under fluoroscopy, when the device is ata rotational orientation opposite to the desired rotational orientation.

FIG. 20 is a schematic view showing the appearance of the radiopaquemarker of the device of FIG. 17 under fluoroscopy, when the device is ata sideways rotational orientation with respect to the desired rotationalorientation.

FIG. 21 is an enlarged bottom plan view of the distal portion of thecatheter of the device of FIG. 17 .

FIG. 22 is a schematic view showing the appearance of the additionalradiopaque marker of the device of FIG. 17 under fluoroscopy, when thedevice is within a desired rotational tolerance.

FIG. 23 is a schematic view showing the appearance of the additionalradiopaque marker of the device of FIG. 17 under fluoroscopy, when thedevice is not within a desired rotational tolerance.

FIG. 24 is a schematic view of a delivery device of an alternativeexample device for endovascular vein puncture.

FIG. 25 is a schematic view of the device of FIG. 24 , in use.

FIG. 26A is a schematic illustration of an ablation catheter having anablation balloon positioned in an intercostal vein for ablation of athoracic splanchnic nerve.

FIG. 26B is a cross sectional view of the device of FIG. 26A.

FIG. 27 is a schematic illustration of an ablation catheter positionedin an intercostal vein for ablation of a thoracic splanchnic nerve.

FIG. 28 is a schematic illustration of an ablation catheter having anablation balloon positioned in an intercostal vein for ablation of athoracic splanchnic nerve.

FIG. 29 is a schematic illustration of an ultrasound ablation catheterpositioned in an intercostal vein for ablation of a thoracic splanchnicnerve.

FIG. 30A is a schematic illustration of an ablation catheter having anablation balloon positioned in an intercostal vein for ablation of athoracic splanchnic nerve.

FIG. 30B is a cross section of the device shown in FIG. 30A.

FIG. 31 is a schematic illustration of an ablation catheter positionedin an intercostal vein for ablation of a thoracic splanchnic nerve.

FIGS. 32A and 32B are schematic illustrations of alternative embodimentsof electrodes having fluid escape features.

FIG. 33 is a schematic illustration of the ablation catheter of FIG. 31positioned at an ostium of an intercostal vein for ablation of athoracic splanchnic nerve.

FIG. 34A is a schematic illustration of an ablation catheter positionedin an intercostal vein for ablation of a thoracic splanchnic nerve.

FIG. 34B is a sectional view of the ablation catheter shown in FIG. 34A.

DETAILED DESCRIPTION

This disclosure is related by subject matter to the disclosure in U.S.Pub. No. 2018/0110561, PCT Pub. No. WO2018/023132, and PCT ApplicationNo. PCT/US2018/066047 (filed Dec. 17, 2018), all of which areincorporated herein by reference in their entireties for all purposes.

The disclosure herein is generally related to methods of treating atleast one of heart failure and hypertension by increasing splanchniccapacitance. Some approaches include systems, devices, and methods fortransvascular (e.g., transvenous) ablation of target tissue to increasesplanchnic capacitance. The devices and methods may, in some examples,be used for ablating one or more splanchnic nerves to increasesplanchnic capacitance. For example, the devices disclosed herein may beadvanced endovascularly to a target vessel in the region of a targetnerve including a thoracic splanchnic nerve (“TSN”), such as apreganglionic greater splanchnic nerve (“GSN”), lesser splanchnic nerve,or least splanchnic nerve or one of their roots (a TSN nerve root). Thetarget vessel may be, for example, an intercostal vein or an azygos vein(or both) or a vein of the azygos vein system, preferably, one or moreof the lowest (i.e., most caudal) three intercostal veins (which may beT9, T10, and T11). A target region in a target vein for example mayinclude a lumen in an intercostal vein, and can be a region that doesnot extend more than 30 mm into the vein from the adjoining azygos orhemiazygos vein, and optionally does not extend more than 20 mm into thevein from the adjoining azygos or hemiazygos vein. The target regionthus has a distal end that is not further than a particular distance (orrange of distances) from the ostium. Methods of use herein that positionan ablation element (or ablation member generally) in a target region ofa vessel are therefore not limited to requiring that the entire lengthof the ablation element is positioned in the target vessel, but ratherthey include methods in which a proximal portion, perhaps a relativelysmall portion thereof (e.g., less than 25% of the length) is stillpositioned in an adjacent vessel (e.g., an azygous vein). Methods hereinthat describe placing an ablation element or member in a target vesselwithin a certain distance from an ostium are therefore generallydescribing positioning a distal end of the ablation element within thetarget region of the target vessel, regardless of whether the entiretyof the ablation element is within the same vessel (e.g., intercostalvein) or whether a portion is disposed in an adjacent vessel (e.g.,azygous vein). In any of the methods herein, less than 50% of the lengthof the ablation element may be positioned in the adjacent vessel, suchas less than 45%, or less than 40%, or less than 35%, or less than 30%,or less than 25%, or less than 20%, or less than 15%, or less than 10%.

A TSN may be up to 5 mm from a target intercostal vein in most humans.Intercostal veins at the lower levels (e.g., T9, T10, T11 levels) mayhave inner lumens in the target regions having a diameter range of 2 to3.5 mm. A TSN, in particular a fully formed GSN, may traverse a targetintercostal vein in the target region between an adjoining azygos orhemiazygos vein and a distance of no more than 15 mm from the adjoiningazygos or hemiazygos. Beyond a distance of 20 mm from the adjoiningazygos or hemiazygos a sympathetic trunk may traverse the intercostalvein.

Ablation of a TSN by thermal coagulation may involve heating tissue withan ablation element positioned in the target intercostal vein, whichpresents various technical challenges. Thermal ablation from a smallvein can cause the vessel to shrink during energy delivery, which candrastically alter the thermal and electrical environment of an ablationelement, particularly if the vessel shrinks around the ablation element,for example caused by a significant change in tissue contact or bloodflow, making energy delivery erratic and ablation less predictable orcontrolled.

With devices and methods disclosed herein, the TSN may be ablated in arelatively safe manner, with minimal or reduced adverse effects (such asdamage to the lungs or other nerves). Some method of use embodimentsherein may temporarily occlude blood flow and reduce an effect of veincollapse, thus advantageously avoiding challenges of a changing thermaland electrical environment during the heating process. Some method ofuse embodiments herein may ablate a nerve up to 5 mm from the targetvessel. Some of the devices herein are dimensioned and configured fordelivery and positioning in vasculature specified for ablating a targetnerve (e.g., TSN, GSN).

Some of the devices herein may have one or more features that providesfor a safe delivery to the target vessel.

Some of the devices and methods of use herein may safely deliver energywith temperature monitored energy delivery.

Some of the methods of use herein may generate a lesion capable oftargeting a nerve up to 5 mm away from the target vessel and within atarget region having a continuous lesion length of up to 20 mm (e.g., 15mm, 12 mm) with a single positioning and delivery of energy.

Some of the devices and methods herein are adapted to avoid risks ofboiling, hot spots, or erratic energy delivery that could decreaseablation efficacy. Furthermore, some embodiments may include nervestimulation to identify a target nerve or non-target nerve to confirmpositioning prior to ablation, or to confirm technical success during orfollowing ablation.

Studies performed to inform this disclosure indicated that the lowestthree intercostal veins are likely best positioned for the placement ofthe medical ablation devices because the TSN, GSN or GSN roots (targetnerves) are very likely to cross one or more of the lowest threeintercostal veins between the ostium to the azygous vein and within aparticular distance from the ostium. One aspect of this disclosure isthus a preferred method that includes positioning the medical devices(at least an ablation member portion thereof) in one of a particularnumber of intercostal veins, and additionally within a particulardistance from the ostium of the azygous vein. This location andplacement will provide the highest likelihood that, when activated, themedical device will effectively ablate the target nerves, described inmore detail below.

It may be preferred, but not required, that the methods of ablationcreate a continuous ablation zone (i.e., not having separate, discreteregions of ablated tissue that are not connected to each other). Thisensures that the region of tissue where the target GSN nerve or GSNnerve root is likely to be located is most likely to be effectivelyablated by the ablation energy. The continuous ablation zone may becircumferential, or less than circumferential.

It may also be preferred, but not required, that the methods of ablationcreate an ablation zone that has a depth of at least 5 mm and a lengthin a range of 5 to 20 mm, and preferably in the range of 10 to 20 mm.Ablation regions or zones with these parameters increase the likelihoodthat the ablation region will include the target GSN or GSN root. Whilethis disclosure generally describes lesions with a length in the rangeof 5-20 mm, it may be possible to effectively ablate a target nerve witha lesion that has a length of less than 5 mm, such as between 1 mm and 5mm. For example, some target nerves may be quite close to an ostiumbetween, for example, an azygous vein and an intercostal vein, and itmay be acceptable to create an ablation region or zone with a length ofless than 5 mm and still effectively ablate the target nerve. Unliketreatments that are targeting nerves that innervate a vessel (e.g., somerenal denervation approaches), these exemplary methods of treatment aretargeting one or more target nerves that are in relatively closeproximity to the intercostal vein and traverse or cross, rather thanfollow, the vein. Traverse in this context does not mean the nervepasses through the vein structure in any way, but rather refers to thegeneral relative orientation of the nerves and veins.

It is understood that while some methods herein create a lesion that hasa length within a particular range, the methods may inherently createthese ablation lengths even if the length of the ablation zone is not adirect input to a procedure. For example, if a console or energygenerator is used to deliver energy, one or more delivery parameters maybe selected as part of the procedure (e.g., time, power, etc.), andablation length is not necessarily an input to the procedure. This meansthat the ablation zone length may occur as a result of a procedure, evenif the length is not particularly selected by a user or is not input toan energy generating device such as a generator. If a result of aprocedure is that a lesion is created with a length in the ranges herein(or even likely to be created with a length in the ranges herein, thenthe method is understood to fall within the scope of a claim thatincludes an ablation zone length.

Endovascular Vessel Puncture Embodiments

Disclosed herein are devices and methods for endovascular vein puncture,and subsequent treatment of a target structure (e.g., a nerve) that isexterior to the vein. The devices and methods may, in some examples, beused for splanchnic nerve ablation for treatment of heart failure. Forexample, the devices disclosed herein may be advanced endovascularly toa target vein in the region of a thoracic splanchnic nerve (TSN), suchas a greater splanchnic nerve (GSN) or a TSN nerve root. The target veinmay be, for example, an intercostal vein or an azygos vein or a vein ofthe azygos vein system. The device may then be activated or deployed topuncture the vein wall of the target vein. The device may then beactivated or deployed again to treat the TSN, for example by temporarilyblocking the TSN or permanently ablating the TSN. Ablation of the TSNmay be carried out, for example, by radiofrequency (RF) ablation,cryoablation, thermal ablation, chemical ablation, or pharmaceuticalablation. Ablation of the TSN may affect circulating blood volume,pressure, blood flow and overall heart and circulatory system functions,as described in Patent Application No. PCT/US2017/044747, in order totreat heart failure. Ablation of the TSN may also have therapeuticbenefits such as treating intractable abdominal pain or motility. Withthe devices and methods disclosed herein, the TSN may be ablated in arelatively safe manner, with minimal or reduced adverse effects (such asdamage to the lungs or other nerves).

Endovascular Vessel Puncture Devices

Referring to FIG. 1 , a first example of a device 100 for endovascularvein puncture is shown. The device 100 includes an elongate catheter102, which extends along a longitudinal axis 104 (also referred toherein as a ‘catheter axis’) (shown in FIG. 2 ) and has a catheterproximal portion 106 and a catheter distal portion 108. The catheterdistal portion 108 may generally function as the working end of thedevice 100. The catheter proximal portion 106 may generally remainexterior to a patient in use, and may be manipulated by a physician orother professional. The catheter 102 has a catheter outer diameter 110(shown in FIG. 2 ).

In some examples, the catheter can include a braided shaft to facilitatetorqueability (i.e., transmission of torque from the catheter proximalportion 106 to the catheter distal portion 108), particularly over atortuous delivery path.

Referring to FIG. 2 , in the example shown, the catheter 102 includes aguidewire lumen (not shown) extending therethrough (along the catheteraxis 104), and the catheter distal portion 108 includes a guidewire exitport 112, so that the catheter 102 can be advanced into the venoussystem along a guidewire. The catheter 102 has a circumferential outersurface 114 and a distal end surface 116, and in the example shown theguidewire exit port 112 is at the distal end surface 116.

In alternative examples, the guidewire lumen and exit port may beomitted, and the catheter may be advanced into a patient'scardiovascular system (e.g., into a vein or artery) without the aid of aguidewire.

The catheter outer diameter 110 may be sized to pass into the azygosvein of a patient, and optionally into the intercostal veins of apatient. For example, the catheter outer diameter 110 may be betweenabout 1 mm and 5 mm, or between about 1 mm and 3 mm.

Referring to FIGS. 2 and 3 , in the example shown, the device 100further includes a needle guide 101, which has a distal end 103 (alsoreferred to herein as a “needle guide distal end”) that is blunt. Theneedle guide 101 is deployable from the catheter 102, from a needleguide storage position (shown in FIG. 2 , in which the needle guide 101is not visible) to a needle guide working position (shown in FIG. 3 ).

In general, the needle guide storage position can be any position inwhich the needle guide distal end 103 is withdrawn towards the catheter102, relative to the needle guide working position. Referring still toFIGS. 2 and 3 , in the example shown, when the needle guide 101 is inthe storage position, the needle guide distal end 103 is nested withinthe catheter. The needle guide 101 is deployable from the catheter 102via a side port 109 in the circumferential outer surface 114 of thecatheter. When in the deployed position, the needle guide 101 extendsfrom the side port 109, so that the needle guide distal end 103 isradially spaced from the catheter 102 (i.e., spaced from the catheter102 in a direction transverse to the catheter axis 104). In the exampleshown, when in the needle guide working position, the needle guide 101is generally straight, and is inclined with respect to the catheter axis104. In alternative examples, the needle guide can be bent or curved,and/or can be perpendicular with respect to the catheter axis 104.

Referring still to FIG. 3 , in the example shown, the needle guide 101is relatively short. That is, in the example shown, when the needleguide 101 is in the needle guide working position, the needle guidedistal end 103 is radially spaced from the catheter by a needle guidedeployed distance 111. In some examples, the needle guide deployeddistance 111 is selected so that when the needle guide 101 is in thedeployed position and abuts a vein wall (e.g., an intercostal vein wall,an azygos vein wall, or a wall of a vein of the azygos vein system), theneedle guide distal end 103 is forced against the vein wall with somepressure (as will be described below). For example, when the needleguide 101 is in the deployed position and abuts a vein wall, it can pushthe catheter 102 to abut an opposing vein wall, which then in turnforces the needle guide distal end 103 against the vein wall. Tofacilitate the application of sufficient pressure by the needle guidedistal end 103 to the vein wall, the catheter diameter 110 plus theneedle guide deployed distance 111 may be equal to or slightly largerthan the inner diameter of a targeted vein, when the needle guide isfully deployed. In situations where a patient's vein diameter is alittle smaller than the combined distance of the catheter diameter 110and the needle guide deployed distance 111, the vein may stretch toaccommodate full deployment of the needle guide 101. For example, such acatheter configured to be used in a human's T10 or T11 intercostal veinmay have a catheter diameter 110 plus needle guide deployed distance 111equal to a distance in a range of 2 mm to 4 mm (e.g., in a range of 2.5mm to 3.5 mm). In another example, such a catheter configured to be usedin a human's azygos or hemiazygos vein at a level of T10 or T11 may havea catheter diameter 110 plus needle guide deployed distance 111 equal toa distance in a range of 3.5 mm to 6.5 mm (e.g., in a range of 4 to 5mm). Optionally, a user may size a target vessel prior to delivering anablation catheter (e.g., with CT angiography or other medical imagingmodality) and select a suitable ablation catheter depending on thediameter of the target vein. In some examples the needle guide deployeddistance 111 is less than the catheter outer diameter 110. For example,the needle guide deployed distance 111 can be between about mm and about6 mm or between about 0.5 mm and about 3 mm, or between about 2 mm andabout 6 mm.

Referring to FIGS. 3 and 4 , in the example shown, the device furtherincludes a needle 105, which has a sharp puncturing end 107. The needle105 is deployable from within the needle guide 101, from a needlestorage position (shown in FIG. 3 , in which the needle 105 is notvisible) to a puncturing position (shown in FIG. 4 ).

Referring still to FIGS. 3 and 4 , in the example shown, when the needle105 is in the needle storage position, it is within the needle guide101, so that the puncturing end 107 is shy of the needle guide distalend 103. When in the puncturing position, the needle 105 protrudes fromthe needle guide 101, so that the puncturing end 107 extends proud ofthe needle guide distal end 103.

Referring to FIG. 4 , in the example shown, the needle 105 is relativelyshort. That is, in the example shown, when the needle 105 is in thepuncturing position, the puncturing end 107 is spaced from the needleguide distal end 103 by a needle deployed distance 113. In someexamples, the needle deployed distance 113 is selected to be long enoughto just puncture a vein wall, such as an intercostal vein wall or anazygos vein wall, without protruding significantly beyond the vein wall.This can allow for accurate puncture of a vein while minimizing orreducing the risk of damaging nearby tissue, such as lung tissue. Forexample, the needle deployed distance 113 can be less than 2 mm, or lessthan 1 mm, or about 0.5 mm. In some examples, the needle deployeddistance 113 is less than the catheter outer diameter 110.

Referring to FIG. 5 , in the example shown, the device 100 furtherincludes a delivery device 115, which can deliver a treatment to apatient. The treatment can in some examples be for nerve ablation, suchas TSN nerve ablation. For example, the delivery device 115 can be afluid delivery device (for delivery of an ablative chemical orpharmaceutical), a thermal energy delivery device (for delivery ofheat), a cryoablative energy delivery device, an electrical energydelivery device, and/or an RF energy delivery device. The treatment canbe delivered circumferentially from the delivery device 115, orlongitudinally (also referred to as ‘directionally’) from the deliverydevice 115.

Referring still to FIG. 5 , in the example shown, the delivery device115 is a probe that has a blunt distal end 117 (also referred to hereinas a ‘delivery device distal end’), which is generally rounded. Thedelivery device 115 further includes a fluid port 118, which is locatedproximally of the blunt distal end 117, on a side wall of the deliverydevice 115. The fluid port 118 can be for delivering a fluid, such as achemical or pharmaceutical ablative agent, an anesthetic, a coolingfluid, or another fluid.

Referring still to FIGS. 4 and 5 , in the example shown, the deliverydevice 115 is deployable from within the needle 105, from a deliverydevice storage position (shown in FIG. 4 , in which the delivery device115 is not visible), in which it is housed within the needle 105 and theneedle guide 101, to a delivery device treatment position (shown inFigure in which the delivery device distal end 117 extends proud of thepuncturing end 107 of the needle. In the example shown, the fluid port118 also extends proud of the puncturing end 107 of the needle.

In the example shown, when in the delivery device treatment position,the delivery device 115 extends proud of the puncturing end 107 by adelivery distance 99. The delivery distance 99 can be selected toposition the delivery device 115 proximate a treatment location. Forexample, if the device 100 is being used to ablate the GSN via punctureof an intercostal vein, the delivery distance 99 can be between about 3mm and about 7 mm, or between about 4 mm and about 6 mm. Alternatively,if the device 100 is being used to ablate the GSN via puncture of anazygos vein or vein of the azygos vein system, the delivery distance 99can be up to 15 mm.

In alternative examples, the delivery device 115 can be omitted. In suchexamples, a treatment may be delivered directly from the needle 105. Forexample, a pharmaceutical agent could be delivered directly from theneedle.

The device 100 of FIGS. 1 to 5 may include one or more radiopaquemarkers, for facilitating advancement, positioning or orientation of thedevice. The radiopaque marker(s) may be, for example, on the catheter,the needle guide, the needle, or the delivery device. For example, thecatheter distal portion 108 may be advanced to a target location in avessel, and prior to deploying a needle guide 101, the user may visuallyassess the rotational orientation of the catheter distal portion 108 byimaging the catheter 102, the radiopaque marker, and/or parts of thepatient's anatomy, using fluoroscopy. This can indicate the direction inwhich the needle guide 101 will deploy.

Referring to FIG. 17 , a device 1700 that includes a radiopaque marker1746 that is configured to facilitate placement of a catheter 1702 at adesired orientation is shown. The device 1700 is similar to the device100, and for simplicity, features that are like those of the device 100will not be described in detail. In the device 1700, the radiopaquemarker 1746 is configured to distinguish when the radiopaque marker 1746is rotationally aimed at a C-arm head. Since the position of theradiopaque marker 1746 is circumferentially aligned with the directionof deployment of the needle guide (not shown), the radiopaque marker1746 can be used to indicate when the needle guide is aimed at a C-armhead. In the example shown, the radiopaque marker 1746 is made from aradiopaque material and is asymmetric in shape. Specifically, theradiopaque marker 1746 is N-shaped. If the radiopaque marker 1746 isfacing towards the C-arm head, the radiopaque marker 1746 will appear asthe letter N, as shown in FIG. 18 . If the radiopaque marker 1746 isfacing away from the C-arm head (e.g., toward the vertebra), theradiopaque marker 1746 will appear as a backwards letter N, as shown inFIG. 19 . If the radiopaque marker 1746 is sideways, the radiopaquemarker 1746 will appear as a line, as shown in FIG. 20 .

Referring to FIG. 21 , in the example shown, the device 1700 furtherincludes an additional radiopaque marker 1748 that is configured tovisually indicate when the rotational position of the catheter 1702 iswithin a set tolerance. Particularly, the additional radiopaque marker1748 includes two lines the center of which is circumferentially spacedfrom the radiopaque marker 1746 by about 180 degrees, so that theradiopaque marker 1746 appears between the lines of the additionalradiopaque marker 1748 when the orientation is within the set tolerance,as shown in FIG. 22 . When the orientation is outside the set tolerance,the radiopaque marker 1746 will overlap one of the lines of theadditional radiopaque marker 1748 or will be outside of the lines of theadditional radiopaque marker 1748, as shown in FIG. 23 . For example,the set tolerance may be up to 45 degrees on either side of perfectalignment (e.g., up to 35 degrees, or 25 degrees, or 15 degrees, or 5degrees).

Referring now to FIGS. 6 to 8 , another example device 600 forendovascular vein puncture is shown. The device 600 is similar to thedevice 100 of FIGS. 1 to 5 , and for simplicity, features that are likethose of the device 100 will not be described in detail. Furthermore, inthe description of device 600, features that are like those of device100 will be referenced with like reference numerals to those of device100, but incremented by 500.

Referring to FIG. 6 , similarly to the device 100, the device 600includes a catheter 602, a needle guide 620 a (also referred to hereinas a ‘first needle guide’) that is deployable from the catheter 602 in adirection that is transverse to the catheter axis 104, and a relativelyshort needle 628 a (also referred to herein as a ‘first needle’) that isdeployable from the needle guide 620. However, the device 600 furtherincludes a second needle guide 620 b that is deployable from thecatheter 602 in a direction that is transverse to the catheter axis 104(this direction may be referred to herein as a ‘second direction’ thatis transverse to the catheter axis), and a second needle 628 b that isdeployable from the second needle guide 620 b. The second needle guide620 b and second needle 628 b are similar in configuration and operationto the first needle guide 620 a and first needle 628 a, and will not bedescribed in detail.

Referring still to FIG. 6 , in the example shown, the first needle guide620 a and first needle 628 a are longitudinally spaced apart from anotch 642 at the distal end 608 by a spacing 609 of between 1.5 cm andabout 2.5 cm, or about 2 cm to coincide with a distance between ananchoring vein and a first target position (e.g., an anchoring vein maybe a T11 intercostal vein in which a guidewire is delivered and a firsttarget position may be in an azygos vein between a T10 and T11intercostal vein). Furthermore, the first needle guide 620 a and firstneedle 628 a are longitudinally spaced apart from the second needleguide 620 b and second needle 628 b. That is, the first needle guide 620a is deployable from the catheter 602 at a first longitudinal positionon the catheter 602, the second needle guide 620 b is deployable fromthe catheter 602 at a second longitudinal position on the catheter 602,and the second longitudinal position is spaced from the firstlongitudinal position. The second longitudinal position may be spacedfrom the first longitudinal position by a spacing 644 of between about 3cm and about 5 cm, or of about 4 cm to coincide with a distance betweentarget positions (e.g., a first target position may be in an azygos veinbetween a T10 and T11 intercostal vein and a second target position maybe in the azygos vein between a T9 and T10 intercostal vein).

Referring still to FIG. 6 , in the example shown, the first needle guide620 a and first needle 628 a are circumferentially aligned with thesecond needle guide 620 b and second needle 628 b. That is, the firstneedle guide 620 a is deployable from the catheter 602 at a firstcircumferential position on the catheter, the second needle guide 620 bis deployable from the catheter 602 at a second circumferential positionon the catheter 602, and the second circumferential position is alignedwith the first circumferential position.

The device of FIG. 6 may allow for the treatment of a relatively largeanatomical area with simplicity, and/or in a relatively short timeframe. That is, a treatment (e.g., an ablative treatment) can bedelivered simultaneously from the first needle 628 a and the secondneedle 628 b, to ablate a large area.

Similar to the device 100, the first needle 628 a and second needle 628b can each optionally house a respective delivery device for deliveringa treatment.

Referring to FIGS. 7 and 8 , similarly to the device 100, the deviceincludes a guidewire lumen, and a guidewire exit port 612 at thecatheter distal end 608. However, the guidewire exit port 612 is a notch642 (also referred to herein as an ‘orienting notch’), and the notch 642is open at both the distal end surface 616 and the circumferential outersurface 614, and between these two surfaces.

In the example shown, the notch 642 is open at a notch circumferentialposition on the catheter. The notch circumferential position can in someexamples be within 30 degrees of the first circumferential positionand/or the second circumferential position. In the example shown, thenotch circumferential position is aligned with the first circumferentialposition and the second circumferential position.

The circumferential positioning of the notch 642 with respect to thefirst 620 a and second 620 b needle guides can be used to facilitatepositioning of the first 620 a and second 620 b needle guides at adesired orientation in use. For example, as will be described in detailbelow, in use, a guidewire can be directed in a particular direction,for example laterally from a first vessel (e.g., a vein or artery) intoa second vessel. The catheter 602 can then be advanced over theguidewire, stopping in the first vein. The catheter 602 can then berotated about the catheter axis 604 until the guidewire falls into thenotch 642. When the guidewire falls into the notch 642, the first 620 aand second 620 b needle guides will be pointed laterally in the samedirection as the second vein.

The device of FIGS. 6 to 8 may include one or more radiopaque markers,for facilitating advancement, positioning and/or orientation of thedevice. The radiopaque marker(s) may be, for example, on the catheter,the needle guide(s), the needle(s), or the delivery device(s). In theexample shown, the distal tip of the catheter (including the distal endsurface 616 and the portion of the circumferential outer surface 614adjacent the notch 642) is radiopaque.

As mentioned above, the devices described herein may include a deliverydevice for delivering a treatment, and the delivery device can delivercryogenic energy (also referred to as cryoablative energy). The use ofcryogenic energy for ablation may be in some examples beneficial, as itmay allow for a controlled and predictable ablation zone (e.g., a zoneextending circumferentially around the delivery device by about 3 to 5mm), may obviate the need to keep freely delivered fluid in a targetzone, may allow for treatment to be better visualized (e.g., because icecan be seen on medical imaging), may be less painful than other ablationmodes, and may be used for temporary nerve blocking. Referring now toFIG. 24 , an example cryogenic energy delivery device 2334 is shown. Forsimplicity, in FIG. 24 , the other features of the device, such as theneedle guide and needles, are not shown.

In the example shown, the cryogenic energy delivery device 2334 includesa first lumen 2350 (also called a supply lumen) for delivery of acryogenic fluid (e.g., liquid nitrogen, such as supercritical liquidnitrogen as described in U.S. Pat. No. 7,921,657) from a source 2358 tothe distal end 2336 of the cryogenic energy delivery device 2334, and asecond lumen 2352 (also called a return lumen) for return of thecryogenic fluid to the source 2358 (e.g., for recycling or for eventualdisposal or venting). In the example shown, the first lumen 2350 isformed by a central tube 2354 within the cryogenic energy deliverydevice 2334, and the second lumen is formed between the central tube2354 and the outer wall 2356 of the cryogenic energy delivery device2334, so that the first lumen 2350 and second lumen 2352 are coaxial. Inalternative examples, the first 2350 and second 2352 lumens may beformed in another manner, for example, by two adjacent tubes within thecryogenic energy delivery device 2334.

In some examples the central tube 2354 and the outer wall 2356 may beformed by stainless steel hypodermic tubes. The distal end 2336 of thedelivery device 2334 may have a dome welded end.

In some examples, the distal end 2336 of the delivery device 2334 mayinclude one or more temperature sensors (not shown). In some examples,the delivery device 2334 may include one or more stimulation electrodes(not shown). For example, the delivery device 2334 may include twospaced apart band electrodes, which may be used in a bipolar mode.

In some examples (not shown), the catheter and/or needle and/or needleguide may be thermally insulated, so that the cryoablation is deliveredonly from the delivery device 2334, and not from other parts of thedevice.

In examples wherein the device includes two needles, two needle guides,and two cryogenic energy delivery devices (such as the device 600), asingle supply lumen may supply both cryogenic energy delivery devices.

Referring still to FIG. 24 , in the example shown, the source 2358 ofcryogenic fluid includes a fluid reservoir 2360, a supply valve 2362between the fluid reservoir 2360 and the first lumen 2350, a pressurerelease valve 2364 at the exit of the second lumen 2352 for venting thereturned cryogenic fluid to atmosphere, and a controller 2366 forcontrolling the supply valve 2362 and the pressure release valve 2364.The controller 2366 may be in communication with a temperature sensor atthe distal end 2336 of the delivery device 2334, and supply of thecryogenic fluid may be automatically controlled in response to thesensed temperature. Alternatively, supply of the cryogenic fluid may bemanually controlled.

In some examples, the delivery device 2334 may cyclically delivercryogenic energy and thermal energy (e.g., using RF). This may be usedfor reversible blocking of a myelinated nerve by delivering thermalenergy to reversibly block the nerve (i.e., by delivering thermal energyfor a relatively short time at a relatively low temperature, e.g.,between 1 min and 4 mins, below 60 power of 2 to 50 W, or below 20 W),then delivering cryogenic energy to reversibly block the nerve (i.e., bydelivering cryogenic energy for a relatively short time and at arelatively high temperature, e.g., above 15 degrees Celsius). The RFenergy may be delivered via the outer wall 2356 of the delivery device2334. Alternatively, the delivery device can include one or moreelectrodes (e.g., two band electrodes) on the outer wall 2356, and theouter wall 2356 can be electrically insulative.

In some examples (not shown), a delivery device similar to deliverydevice 2334 may be used in a device that does not include a needle guideor a needle, in order to deliver cryogenic energy without puncturing avein. In such a device, RF energy may be used to warm the vein andshrink it around the cryogenic energy delivery device before cooling, sothat blood flow is reduced (which impedes cooling power). Alternatively,occluding balloons may be deployed distal and proximal to the cryogenicenergy delivery device, to stop blood flow from impeding cooling.

The devices described above can optionally include various sensors andelectrodes. For example, the devices 100 and/or 600 can include one ormore temperature sensors and/or bio-impedance sensors. For furtherexample, the devices 100 and/or 600 can include one or more electricalstimulation electrodes. Such sensors and electrodes can be positioned onthe catheter, the needle guide(s), the needle(s), and/or the deliverydevice(s). Such sensors and electrodes are described in detail in PatentApplication No. PCT/US2017/044747.

In any of the above examples, the delivery devices (e.g., deliverydevice 115) can be configured to be flexible, so that if contact with alung occurs, the delivery device can bend to accommodate movement of thelung, to minimize or reduce damage to the lung. For example, if aflexible delivery device contacts or even punctures the lung, movementof the lung can result in flexing of the delivery device, instead oftearing of the lung. For example, a flexible delivery device may includea flexible shaft with sufficient axial compression strength to allow itto be advanced through soft tissue, such as fat, as it is advancedtoward a target, and the flexible shaft may be a coiled spring.

Methods of Using Endovascular Vessel Puncture Devices

Certain anatomical structures of the thorax will be referenced below.These anatomical structures are described and shown in detail in US Pub.No. 2018/0110561, PCT Pub. No. WO2018/023132, and PCT Application No.PCT/US2018/066047 (filed Dec. 17, 2018), which are fully incorporated byreference herein for all purposes.

In the context of this document, the TSN can mean right or left thoracicsplanchnic nerve and their contributing nerves, and endovascularpuncture and treatment (e.g., ablation) can be performed from the azygosvein or one or more intercostal veins to access the right thoracicsplanchnic nerve, or from the hemiazygos vein or intercostal veins toaccess the left thoracic splanchnic nerve, or from their respectivetributaries, or a bilateral treatment can be performed from both theazygos and hemiazygos veins and their tributaries to access both rightand left thoracic splanchnic nerves.

A first example method for endovascular puncture and treatment will bedescribed with reference to FIGS. 9 to 13 . The method will be describedwith reference to the device 100 of FIGS. 1 to 5 . However, the methodis not limited to the device 100, and the device 100 is not limited touse according to the method.

In the example shown, the method is for endovascular puncture of anintercostal vein, and treatment of the GSN by ablation. The method isshown in the T10 intercostal vein. In alternative examples, the methodmay be carried out in other intercostal veins, such as the T9 or T11intercostal vein, examples of which are described herein. Ablation ofthe GSN may be for the purpose of treating heart failure or otherrelated conditions, as described in US Pub. No. 2018/0110561, PCT Pub.No. WO2018/023132, and PCT Application No. PCT/US2018/066047 (filed Dec.17, 2018). In alternative examples, similar methods can be used forendovascular puncture of other vessels, for other treatment purposes.

The intercostal vein may be accessed endovascularly by severalapproaches, including from a subclavian vein, a jugular vein, or afemoral vein. Various approaches are described in US Pub. No.2018/0110561, PCT Pub. No. WO2018/023132, and PCT Application No.PCT/US2018/066047 (filed Dec. 17, 2018), and will not necessarily bedescribed in detail herein.

Referring now to FIG. 9 , as a first step, a guidewire 900 may beadvanced through the patient's venous system, into the T10 intercostalvein 902. The catheter distal portion 108 may then be advanced over theguidewire 900 through the venous system and into the T10 intercostalvein 902, to a target location within the T10 intercostal vein 902. Insome examples, the target location is up to about 3 cm into the T10intercostal vein 902. In some examples, wherein the treatment is forablation of the GSN 904, and wherein damage to the sympathetic chain isto be avoided, the target location may be up to about 1.5 cm into theT10 intercostal vein 902 from the azygos vein 906, or up to about 1 cminto the T10 intercostal vein 902. In some examples, the catheter 102may be advanced by about 3 cm or greater into the T10 intercostal vein,and then a stimulation pulse may be applied from the catheter 102. Ifthe pulse stimulates the sympathetic chain, the catheter can bewithdrawn slightly. Stimulation and withdrawal can be repeated until thestimulation pulse stimulates the GSN without stimulating the sympatheticchain.

In some examples (not shown), a radiopaque marker (such as radiopaquemarkers 1746 and 1748 described above) of the catheter 102 may be usedto facilitate placement of the catheter 102 at a desired rotationalorientation. The desired orientation may be the orientation in which theneedle guide 101 will deploy in a radial direction that is away from thevertebra (e.g., opposite the vertebra) and towards the TSN. For example,if the target vessel is a right T11 intercostal vein, a C-armfluoroscope may be centered on a T11 vertebra, and optionally rotatedfrom an anterior-posterior center position (AP position) to thepatient's right side to obtain an angle that is approximately orthogonalto the tangent of the vertebra. In this position, it can be desired tohave the needle guide 101 deploy in a radial direction toward the C-armhead, which is where the GSN often traverses the intercostal vein. Thecatheter 102 may be torqued to rotate the catheter distal portion 108within the intercostal vein until the radiopaque marker indicates thatthe needle guide 101 will be deployed toward the C-arm and thus towardthe target nerve.

Since the GSN is often between the intercostal vein and the parietalpleura, and the pleura in this location often has approximately the samecontour as the vertebral column, deploying the needle guide 101orthogonal to the tangent of the vertebra can direct the needle guideorthogonal to the pleura. Even though the needle 105 punctures only aslight amount past the vein wall, and the delivery device 115 can have ablunt end, there may still be a small risk of puncturing through theparietal pleura, in which case the fluid or energy may not beeffectively delivered to the GSN. By delivering the needle 105 ordelivery device 115 at an oblique angle (e.g., about 45 degrees) insteadof orthogonal, the risk of puncturing the pleura can be reduced. Thus,in alternative examples, a catheter may include a radiopaque marker thatis circumferentially spaced from the needle guide, so that when theradiopaque marker is aimed at the C-arm head, the needle guide deploysin a direction that is not aimed at the C-arm head (e.g., 45 degreesaway from the C-arm head.

Referring to FIGS. 10 and 11 , the needle guide 101 may then be deployedfrom the catheter 102. As discussed above in the “Devices” section, theneedle guide 101 can be deployed in a direction that is transverse tothe catheter axis 104 (shown in FIG. 1 ), so that the needle guidedistal end 103 is radially spaced from the circumferential outer surface114 of the catheter 102. The needle guide 101 can be deployed until theneedle guide distal end 103 contacts the vein wall 908, as shown in FIG.10 . Continued deployment can cause the needle guide distal end 103 tobe forced against the vein wall 908 (in preparation for deployment ofthe needle 105). For example, continued deployment can cause thecatheter 102 to be pushed away from the vein wall 908, so that thecatheter 102 abuts the opposing wall 910 of the vein 902 (also referredto herein as an ‘opposing vein wall’), as shown in FIG. 11 , or contactsanother anatomical structure. Alternatively, continued deployment cancause other movement of the catheter 102 which results in the distal end103 applying pressure to the vein wall 908 in preparation for deployingthe needle 105.

Referring to FIG. 12 , when the needle guide distal end 103 is forcedagainst the vein wall 908 (e.g., as a result of the catheter 102abutting the opposing vein wall 910 or another anatomical structure),the needle 105 may be deployed from the needle guide distal end 103, topuncture the vein wall 908 with the sharp puncturing end 107 of theneedle 105. Due to the relatively short puncturing distance of theneedle 105, the vein wall 908 can be punctured accurately whileminimizing or reducing the risk of puncture of the lungs or other nearbytissues. For example, as noted above, the needle 105 can be deployed toa deployed distance that is less the catheter outer diameter 110 (shownin FIG. 2 ), and/or that is less than 2 mm, or less than 1 mm, or about0.5 mm.

When the vein 902 has been punctured, various optional steps can becarried out. For example, a nerve stimulation test can be carried out,by delivering an electrical stimulation pulse via the sharp puncturingend 107, in order to confirm the position of the sharp puncturing end107 with respect to the GSN 904 or other nerves or anatomicalstructures. For further example, a contrast agent can be delivered toconfirm that the lung or parietal pleura has not been punctured.

A treatment may then be delivered to the region exterior to the vein902, via the sharp puncturing end 107 of the needle 105. In the exampleshown, the delivery device 115 is deployed from the puncturing end 107and is used to deliver the treatment. In alternative examples, theneedle 105 itself may deliver the treatment. For example, a fluid (suchas an ablative fluid) may be delivered via the needle.

Referring to FIG. 13 , as mentioned above, the delivery device 115 canbe deployed from the puncturing end 107 by a delivery distance 99 (shownin FIG. 5 ). Depending on the mode of treatment, the delivery distance99 can be, for example, up to 15 mm, or between 3 mm and 7 mm, orbetween 4 mm and 6 mm. In many situations, in order to ablate the GSN904 from an intercostal vein using RF energy, the delivery device 115can be deployed by between 4 mm and 6 mm. Optionally, a nervestimulation test can be carried out by delivering a pulse via thedelivery device 115, in order to confirm the position of the deliverydevice 115 with respect to the GSN 904 or other nerves or anatomicalstructures.

A treatment can then be delivered from the delivery device 115. Forexample, as mentioned above, a treatment fluid can be delivered, or athermal energy treatment can be delivered, or a cryogenic energytreatment can be delivered, or an RF energy treatment can be delivered.

Upon completion of treatment, the device 100 may be withdrawn from thepatient, by retracting the delivery device 115 towards the needle 105,retracting the needle 105 towards the needle guide 101, and retractingthe needle guide 101 towards the catheter 102, and then withdrawing thecatheter distal portion 108 through the venous system of the patient.

Referring now to FIGS. 14 to 16 , another method for endovascularpuncture and treatment will be described. The method will be describedwith reference to the device 600 of FIGS. 6 to 8 . However, the methodis not limited to the device 600, and the device 600 is not limited touse according to the method.

In the example shown, the method is for endovascular puncture of theazygos vein 906 at the T9 to T11 level on the right side, and treatmentof the GSN 904 by ablation. The azygos vein 906 may be accessedendovascularly by several approaches, including from a subclavian vein,a jugular vein, or a femoral vein. Various approaches are described inInternational Patent Application No. PCT/US2017/044747, and will not bedescribed in detail herein.

Referring now to FIG. 14 , in the example shown, as a first step, aguidewire 900 may be advanced through the patient's venous system.Although the azygos vein 906 is the target for puncture, the guidewire900 may be advanced through the azygos vein 906 and into the T11intercostal vein 912. The catheter distal portion 608, may then beadvanced over the guidewire 900 through the venous system and into theazygos vein 906, to a target location within the azygos vein 906. Insome examples, the target location may be between the T9 and T11 level.For example, the catheter distal portion 608 may be positioned so thatthe first needle guide 620 a (shown in FIG. 16 ), when deployed, isbetween the T10 intercostal vein 902 and the T11 intercostal veins 912and so that the second needle guide 620 b, when deployed, is between theT9 intercostal vein (not shown) and T10 intercostal vein 902.

Referring to FIG. 15 , when the catheter distal portion 608 is at thetarget location, its orientation may be adjusted so that when deployed,the first 620 a and second 620 b needle guides (shown in FIG. 16 ) aredirected towards the GSN 904. On the right side of the body, theintercostal veins are generally on the same side of the azygos vein 906as the GSN 904 and approximately in the same plane as the GSN 904, andthe placement of the guidewire 900 in the T11 intercostal vein 912 canfacilitate adjustment of the rotational orientation of the catheter 602.That is, with the guidewire 900 in the T11 intercostal vein 912 and thecatheter distal portion 608 at the target location in the azygos vein906, the catheter 602 can be rotated about the catheter axis 604. Whenthe notch 642 in the catheter distal portion 608 is oriented in the samedirection as the T11 intercostal vein 912—i.e., towards the GSN 904—theguidewire 900 will fall into the notch 642, and will nest into theportion of the notch 642 that is open at the circumferential outersurface 614. This positioning of the guidewire 900 (i.e., nested intothe portion of the notch 642 that is open at the circumferential outersurface 614) can be confirmed under fluoroscopy.

In alternative examples, a device may be used in which the notch and thefirst and second needle guides are circumferentially spaced apart byabout 30 degrees. This can reduce or minimize the risk of puncturing alung, since the first and second needle guides will be directed slightlyaway from the lung and towards the vertebrae.

Referring to FIG. 16 , with the orientation of the catheter 602confirmed, the first 620 a and second 620 b needle guides can bedeployed from the catheter 602, either sequentially or simultaneously.As described above, the first 620 a and second 620 b needle guides canbe deployed until the blunt needle guide distal ends 622 a, 622 b,respectively, contact the azygos vein wall 916, and until the catheter602 is pushed to abut the opposing azygos vein wall 918. The first 628 aand second 628 b needles can then be deployed, in order to puncture theazygos vein wall 916.

Optionally, first and second delivery devices can then be deployed fromthe first 628 a and second 628 b needles and can be used to deliver atreatment. For example, referring to FIG. 25 , cryogenic energy deliverydevices 2334 (as described above with respect to FIG. 24 ) can be usedto deliver cryogenic energy. In some examples, the cryogenic energydelivery devices 2334 can be deployed by a delivery distance of up to 15mm, in order to treat the GSN 904 from the azygos vein 906.

Alternatively, the first 628 a and second 628 b needles themselves canbe used to deliver a treatment.

In any of the above examples, various techniques may be employed toavoid puncture of the lungs or other damage to the lungs by the needlesor delivery devices. For example, a patient may be instructed to holdtheir breath briefly during the procedure, to keep the lungs spaced fromthe device. Alternatively or in addition, various sensors may beemployed to detect lung movement (e.g., flow sensors, bioimpedancesensors, pressure sensors). Such techniques are described in US Pub. No.2018/0110561, PCT Pub. No. WO2018/023132, and PCT Application No.PCT/US2018/066047 (filed Dec. 17, 2018), and will not be described indetail herein.

In any of the above examples, where heat is being used for ablation ofthe GSN (e.g., by direct thermal treatment or by RF energy treatment),blood flow in the area of the GSN (e.g., blood flow in the azygos vein)may interfere with the treatment by cooling the area. In some suchexamples blood flow to the area of the GSN may be blocked, or may bedirected away from the area of the GSN. For example, a balloon may beinflated in the azygos vein in near the ostium of the intercostal vein.Such techniques are described in US Pub. No. 2018/0110561, PCT Pub. No.WO2018/023132, and PCT Application No. PCT/US2018/066047 (filed Dec. 17,2018), and will not necessarily be described in detail herein.

In any of the above examples, wherein a treatment fluid is delivered,the fluid can optionally have a viscosity that is or can becomerelatively high, so that the fluid remains in the area of the GSN. Forexample, the fluid can have a viscosity that is initially relatively low(e.g., at room temperature or below), but that increases in viscosity atbody temperature. Alternatively, the fluid can be provided as twoseparate components, via two separate lumens in the device. The fluidcomponents may have a relatively low viscosity, but upon being combined,may increase in viscosity.

In any of the above examples, after the ablation treatment is complete,a stimulation may be carried out to confirm that the GSN has beenablated. Such stimulation is described in US Pub. No. 2018/0110561, PCTPub. No. WO2018/023132, and PCT Application No. PCT/US2018/066047 (filedDec. 17, 2018), and will not be described in detail herein.

In any of the above examples, the catheter may be advanced through thevenous system through a delivery sheath.

In any of the above examples, upon retraction of the device from thepatient, a substance may be injected via the device in order to promotehealing of the puncture in the vein.

While the above description provides examples of one or more processesor apparatuses, it will be appreciated that other processes orapparatuses may be within the scope of the accompanying claims.

Transvascular Nerve Ablation Embodiments

There are several devices on the market or in development and disclosedin patent applications that are specifically configured fortransvascular ablation of nerves for renal denervation for treatinghypertension. These devices are designed for use in the renal arteries,and are designed to target nerves that are innervating the renalarteries. Some of the energy modalities that are used in these devicescould theoretically be used for GSN ablation from within an intercostalvein. These devices, however, are not suitable for placement in anintercostal vein and for GSN ablation from within an intercostal vein.This disclosure appreciates this and addresses how one or more aspectsof these devices and methods of use would need to be modified to performtherapies herein.

For example, a renal artery has a diameter of about 5 mm whereas anintercostal vein has a diameter of about 3 mm. This difference indiameter may require downsizing of device components such as electrodes,catheter shafts or deployable structures such as balloons. Furthermore,the intercostal vein contains significantly lower blood flow than arenal artery. Some renal denervation devices rely on blood flow to coolablation energy delivery elements so they function properly. Therefore,some devices may need to be modified to consider lower blood flow. Forexample, a GSN ablation device may require active cooling by irrigatingablation elements or delivering cooling agents to the vessel, ordifferent energy delivery parameters for example lower power for longerduration. Renal denervation devices aim to ablate nerves that reside inthe adventitia of the renal artery in an unpredictable pattern aroundthe artery and target ablation zones may only need to be less than 3 mmdeep. Conversely, GSN ablation from an intercostal vein aims to ablate alarger nerve that is farther away from the vessel and a target ablationzone may need to be up to 5 mm deep. Furthermore, a renal denervationablation pattern typically comprises a number of ablations spread apartlongitudinally and circumferentially, for example in a helical pattern.Circumferential ablations are generally avoided in renal denervation.Whereas, such patterns deployed in an intercostal vein may miss a targetGSN. In transvascular renal denervation a catheter may be advanced froma femoral artery through an aorta and into a renal artery. The size ofthe aorta and renal artery allow a larger bend radius than the size ofan azygos vein and intercostal vein. Thus, a device intended for GSNablation may need to be more flexible and capable of traversing asmaller bend radius compared to renal denervation devices. Some specificmodifications to existing renal denervation devices to make them moresuitable for GSN ablation are discussed further herein.

Vessix Vascular has previously disclosed balloon ablation catheterswhich are described for example in U.S. Pat. Nos. 9,028,472, 9,037,259,9,174,050, 9,566,114, 9,592,386, 9,072,902, which are incorporated byreference herein and contain many features useful for transvascularablation of tissue. To be suitable for GSN ablation from within anintercostal vein, modifications to these devices and methods arerequired.

One embodiment of a transvascular ablation catheter 241 for ablating aTSN or GSN from within an intercostal nerve is shown in FIG. 26A. Thedevice 241 may include a catheter extending along a longitudinal axis.An expandable member, for example in the form of a balloon, 242 havingan unexpanded state and an expanded state may be coupled to a distalregion 243 of the catheter. The expandable member or balloon may have acircumferential treatment zone 248 (e.g., having a length in a range of12 to 20 mm) extending along the longitudinal axis in the expanded stateand surrounding the vessel 55. An electrode assembly 252 comprising aplurality of electrode pads 244 may be mounted to the balloon 242. Eachelectrode pad assembly may include a substrate supporting first andsecond electrode pads with each electrode pad having a pair of elongatebipolar electrodes and connected with an electrical trace 249. Theelectrode pads of each electrode pad assembly may be longitudinally andcircumferentially offset from one another. The method may also includeexpanding the balloon in the intercostal vein so as to electricallycouple the electrodes with a wall of the intercostal vein and drivingbipolar energy between the electrodes of each bipolar pair so as totherapeutically alter the TSN or GSN within 5 mm of the intercostal veinsuch that the blood volume of the patient is redistributed for treatmentof diseases such as pulmonary hypertension, or heart failure.

Each electrode pad may include a temperature sensor disposed between theelectrodes of the pair. The expanding of the balloon may couple thetemperature sensors with the wall of the intercostal vein. In someembodiments, the method may further include directing the energy to thebipolar pairs in response to a temperature signal from the temperaturesensor so as to heat the wall approximately evenly.

To create an ablation having a depth of 5 mm to target a GSN from anintercostal vein the electrode pads may be cooled to allow greater powerto be delivered without desiccating tissue of the vein wall, whichimpedes ablation depth. The electrodes may be cooled for example, bycirculating coolant in the balloon 242. In one embodiment coolant may beinjected into the balloon 242 from a coolant injection port 246 at oneend of the balloon chamber and the coolant may exit the chamber throughan exit port 247 at the opposing end of the chamber and allowed toreturn through the catheter through an exit lumen.

In another embodiment coolant may be deposited into the blood streaminstead of returning through a lumen in the catheter. This embodimentmay allow a thinner, more flexible catheter shaft or a larger coolantdelivery lumen to increase flow rate of the coolant. A coolant exit portmay be smaller than the coolant injection port to allow pressure toincrease in the balloon to inflate it. The coolant exit port may be incommunication with a lumen that does not pass through the full cathetershaft to the proximal end but instead passes to the distal end of thecatheter to deposit the coolant (e.g., normal saline) into theintercostal vein. Optionally the coolant exit lumen may be the samelumen as a guidewire delivery lumen.

Electrode pads may be positioned around the balloon to make acircumferential ablation pattern that is as long as the target ablationzone 58 (e.g., up to 20 mm, about 15 mm, between 12 and 18 mm). Forexample, as shown in FIG. 26B a balloon with electrode pads mounted toan elongate shaft 253 may have an undeployed state having a diameter ofabout 1 mm to 2.5 mm and a circumference of about 3.14 mm to 7.85 mm andbe expandable to a deployed state having a diameter in a range of about3 mm to 5 mm and a circumference in a range of about 9.4 mm to 15.7 mm.Electrode pads 244 may be separated by a distance 250 of less than 5 mm(e.g., less than 2.5 mm) and width or arc length 251 in a range of 3 mmto 3.5 mm. Electrode pads 244 may have a length of about 3 to 5 mm each.As shown in FIG. 26A an electrode pad assembly 252 may comprise multipleelectrode pads 244 arranged on four separate rows connected together byelectrical traces 249, the rows evenly spaced around the circumferenceof the balloon 242 (e.g., four rows at each 90 degree quadrant).Longitudinally, the pads 244 on one row may be offset from pads ofadjacent rows. When the balloon is in its unexpanded state the spacebetween the electrode pads is decreased (e.g., to about 0 to 1 mm) andthe adjacent rows interlock with one another. In its expanded state thespace 250 between the pads expands due to the expandable balloon 242 toabout 2 mm to 5 mm. The balloon 242 may be a compliant material such aslatex or a non-compliant material that flexibly folds to contract.

Alternatively, electrode pads may be positioned only on one side (e.g.,50%, 40%, 30%, 25% of the balloon's circumference) to generate adirectional ablation pattern that is all toward the same side and of alength of the target ablation zone 58. For a directional ablationcatheter a radiopaque marker may be positioned on the distal region ofthe catheter to indicate radial direction. For example, a radiopaquemarker may be asymmetric and positioned on the same side or opposingside as the directional electrode pads to indicate and in use aphysician may torque the catheter to aim the radiopaque marker and thusthe electrode pads away from the vertebra, which is always toward theGSN. FIG. 26A shows several small electrode pads. Alternatively, thedevice may have larger and fewer electrode pads, for example two orthree directional electrode pads (e.g., 3 to 5 mm long) on the same sideof the balloon that span the target ablation zone 58. A gap (e.g., 1 to3 mm) between electrode pads may facilitate bending of the device totraverse from the azygos vein to the intercostal vein.

Just proximal to the balloon the catheter shaft may comprise a flexibleneck 245 that allows the ablation balloon to sit in the intercostalvein's natural orientation. Given the small bend radius at this locationa stiff shaft could apply force to the ablation balloon causing it todistort the intercostal vein and reduce predictability of ablation zone.A flexible neck may be made of a softer durometer polymer (e.g., Pebax)and may have a wire coil embedded in the material, which may allowflexible bending while providing pushability.

The electrode(s) that are most proximal are intended to be placed justin the intercostal vein near the ostium. Blood flow through the azygosvein may metabolically cool tissue near it impeding ablation creation. Alarger amount of ablation power (e.g., RF) or longer duration may bedelivered to this proximal electrode(s) than the rest of theelectrode(s) to compensate for the blood flow cooling.

Medtronic/Ardian Inc. has disclosed a catheter for renal denervationhaving several electrodes mounted along the length of a distal sectionof a catheter shaft that forms a spiral shape when deployed in a renalartery, for example U.S. Pat. No. 9,125,661, US2012/0143293, thedisclosures of which are incorporated by reference herein and containmany features useful for transvascular ablation of tissue. To besuitable for GSN ablation from within an intercostal vein, modificationsto these devices and methods are required. This device has electrodesthat are quite small and thin which result in ablations no deeper than 3mm, relies on blood flow similar to renal artery blood flow to avoidtissue charring, electrode spacing and the helical formation of theshaft would create an ablation pattern that is not suitable for GSNablation because the target nerve could be missed.

FIG. 27 shows a catheter 200 having an elongated shaft 205 with aproximal region and a distal region and an ablation assembly 211 mountedto the distal region. To modify the catheter 200 to be suitable for GSNablation, electrodes 201 may be increased in size (e.g., 2 to 3 mmdiameter 202), and spacing 203 between electrodes may be decreased(e.g., 2 to 4 mm apart). The length 204 of electrodes may remain in the1 to 2 mm range or be increased to the 3 to 4 mm range. The helical formof the shaft is not necessary in the intercostal where a straight shaftis preferred when the electrodes have a diameter 202 close to thediameter of the vessel lumen. Electrodes positioned along the straightportion 209 may span a distance of up to 20 mm (e.g., 18 mm, 15 mm) tocover the target ablation zone 58. Electrodes 201 are mounted to atubular shaft 205. The shaft material in the distal region does not needto be stiff with elastic properties to create a helical preformed shapebut instead may be quite flexible to facilitate delivery over the smallbend radius from the azygos vein to intercostal vein. Optionally theshaft may have a section 210 that elastically forms a loop shape that isproximal to the straight portion 209 intended to be placed in theintercostal vein 55. The loop shape may comprise electrodes 206 and maybe intended to be positioned against the ostium 59, which may ablatetissue around the ostium where a target nerve may reside and also act asa depth stopper to position the straight portion 209 at the correctdepth (e.g., 10 to 20 mm) in the intercostal vein 55. RF ablation energymay be delivered in unipolar mode sequentially or simultaneously andoptionally may be delivered in bipolar mode as well, to achieve bothdeep (e.g., 5 mm) ablations and contiguous ablations. Optionally, RF maybe delivered with a pulsing waveform that allows surface tissue to coolslightly during pauses while deeper tissue cools slower facilitatingablation depth of the targeted 5 mm. Optionally, the electrodes may beirrigated. For example, the electrodes or sections of shaft between theelectrodes may have irrigation ports 207 for delivering fluid such asnormal saline. Optionally, the catheter 200 may have a guidewire lumen208 for delivery over a guidewire 79.

Covidien has disclosed a renal denervation catheter and method of usehaving a deployable balloon with a flexible RF electrode mounted in aspiral configuration to the balloon further comprising apertures thatweep liquid such as a cooling saline or anaesthetic, for exampleUS2015/0105659 which is incorporated by reference and contains manyfeatures useful for transvascular ablation of tissue. To be suitable forGSN ablation from within an intercostal vein, modifications to thesedevices and methods are required. An ablation catheter 180 is shown inFIG. 28 positioned in situ. The distal region 181 of the catheter has anablation assembly 190 wherein an inflatable balloon 182 is mounted to anelongate tubular shaft 183. The dimensions of the balloon may be alteredto fit an intercostal vein (e.g., 2.5 to 4 mm diameter in its inflatedstate) and span a length in a range of 12 to 30 mm. The spiral shape ofthe electrode of the Covidien device may miss the targeted GSN. Theelectrode 184 may be altered to be straight and parallel to the axis ofthe balloon and cover a segment (e.g., 50%, 40%, 30%, 25%) of theballoon's circumference for directional ablation. The electrode 184 mayhave a length 189 in a range of 12 to 20 mm (e.g., up to 20 mm) capableof creating an ablation the length of the target ablation zone 58. Thedistal region 181 may have a radiopaque marker 186 that is radiallyidentifiable to confirm the electrode 184 is oriented toward theanterior of the body where the target GSN 52 passes over the intercostalvein 55. Alternatively, one or more electrodes may be positioned aroundthe balloon for circumferential ablation, such as one or more electrodescarried by the balloon and disposed orthogonal to a longitudinal axis ofthe balloon. The electrode strip 184 may contain Irrigation ports 185over its surface for weeping of fluid. Fluid apertures may be increasedin size to allow greater flow rate. Optionally, the shaft 183 may have aflexible neck 187 within mm proximal of the balloon 182 to allow thedistal region 181 to sit well in the intercostal vein. Optionally, thecatheter 180 may have a guidewire lumen 188.

Recor Medical has disclosed a renal denervation device and method of usethat utilizes ultrasound to ablate tissue around a renal artery, forexample US2015/0290427, US2014/0031727, which are incorporated byreference and contain many features useful for transvascular ablation oftissue. The ultrasound transducer is contained in a balloon that centersthe transducer in the vessel. The transducer is cylindrical and createsa circumferential ablation around the vessel. Cooling fluid is injectedinto the balloon to cool the transducer. The ablations made from thisdevice are about 5 mm long.

Ultrasound ablation has a potential to direct energy and is primarilylimited by the ultrasonic transducer size in relation to the ablationenergy delivery parameters dictating energy dose expressed in terms offrequency, power and time. A frequency between 10 and MHz and power ofabout 1 to 10 Watts may be required to effectively ablate the nerves inabout 2 to 20 seconds from a small transducer (e.g., 5 mm long, 1.5 mmdiameter, cylindrical transducer) located in an intercostal vein toablate a nerve up to 5 mm from the intercostal vein. At these settingssignificant heating of the ultrasound transducer may be mitigated forexample by circulating fluid in an enclosed chamber around theultrasound transducer, or alternatively by allowing blood flow tocontact an open surface biocompatible transducer or a cooling membranein which local heat generated by the vibrating ultrasound transducer maybe used as a part of the controlled ablation cycle. The heat produced byan ultrasound transducer could be dissipated inside the vein and couldalter the temperature field around the ultrasound transducer. Theresulting effect of combining such conductive heating and activeultrasound ablation may provide an effective way of creating a necroticregion in vicinity of any small vessel. Thermal dissipation is arequirement for proper functioning of an ultrasound transducer andcaution should be taken to avoid elevated risk of vessel wall damage.Careful titration of ultrasound energy while taking into account thermaldissipation of local heat constitutes an innovative and more rigorousendovascular ablation approach especially when efficient and collateraldamage free ablation of nerves is the procedure goal.

In an alternative embodiment diagnostic and therapeutic ultrasound maybe delivered from a transducer extracorporally to the target ablationzone. The vicinity of intercostal veins to the outside of the patientmakes feasible the consideration of delivering external ablation througha space between the ribs. The ultrasound transducer may fit in a palmand operate at a frequency window between 3 and 10 MHz by directingenergy into the vasculature using a set of anatomical reference points.Specifically, almost 90 degree angle at the ostia of intercostal veinsfrom an azygos vein present reliable references for a Doppler signalvisualization of the blood stream normal to the direction of ultrasoundpulses emitted by externally placed transducers, which may focusablative ultrasound energy to the target ablation zone. Thus, ostialocations enable anatomical references for further targeting of thegreater splanchnic nerve in between T11 and T10 vertebrae or T9 and T10vertebrae. Extracorporeal ultrasound may furthermore be used to detectthe lung that is in proximity to the target ablation zone and titrateenergy delivery to avoid injuring the lung. In one example, ablativeenergy is delivered when the lung is moved away from the target ablationzone during exhale (e.g., greater than a threshold distance of 10 mm forexample) and decreased or paused when the lung is close to the targetablation zone (e.g., within the threshold distance of 10 mm forexample).

FIG. 29 shows a catheter 220 having an elongate shaft 231 with aproximal region and a distal region and an ablation assembly 232 mountedto the distal region. To modify the device for GSN ablation from withinan intercostal vein an ultrasound ablation catheter 220 has aninflatable balloon 221 which may have a geometry suitable for expansionin an intercostal vein (e.g., outer diameter 222 in a range of 3 to 4 mmin its inflated state) and a length 223 in a range of 12 to 30 mm.Within the balloon 221 multiple ultrasound transducers 224 arepositioned on a shaft 233 centered in the balloon 221. The transducers224 may be placed serially spanning a length 226 that is in a range of12 to 20 mm to generate an ablation of a similar length capable ofcreating an ablation the length of the target ablation zone 58. Due tothe small diameter of the intercostal vein the reduced balloon size mayrisk contacting the transducer or getting over heated by the transducer,which may rupture the balloon or reduce efficacy of the ablation. Toremedy this risk struts or protrusions 227 may be positioned between thetransducer and balloon. The struts 227 may be for example polymerstrands elastically pre-shaped to radially expand away from thetransducers 224. To make a longer ablation to span the targeted ablationzone multiple transducers may be incorporated (e.g., three 4 mm longtransducers) and spaced apart with flexible gaps 228 between them tofacilitate traversing the small bend radius from the azygos vein tointercostal vein. For example, shaft 225 may be a braid reinforcedpolyimide tube with an optional guidewire lumen 229 for delivery over aguidewire 79 and carry electrical conductors that energize thetransducers 224. The ultrasound transducers 224 may be cylindrical forproducing circumferential ablation around the target vein.Alternatively, the ultrasound transducers may be flat or hemicylindricalto produce an ablation that is a partial segment of the circumference ofthe vein and a radially identifiable radiopaque marker 230 may bepositioned on the distal region allowing a user to orient the directionof ablation toward the patient's anterior where the GSN passes over thevein 55. Optionally, the ultrasound transducer may be configured toimage as well as ablate and the imaging function may be used to assessnearby structures such as the lung, vertebra, ribs. Imaging ultrasoundmay be used to confirm the transducer is aiming toward the lung, whichis the direction of the target GSN. Optionally, the shaft may have aflexible neck 231 within 10 mm proximal of the balloon 221 to allow thedistal region to sit well in the intercostal vein.

In an alternative embodiment of an ultrasound ablation catheter, thecatheter can be composed of an active ultrasound transducer and aninflatable reflector balloon, which may be on the same catheter oralternatively be on separate catheters. The reflector balloon may havean inflated diameter in a range of 2.5 to 4 mm and on its proximalsurface have a shape such as a concave curvature that focuses reflectedwaves on to the target ablation zone. The reflector balloon is locateddistal to the transducer and is inserted in the narrower intercostalvein, while the ultrasound transducer remains in the larger azygos vein.The ultrasound transducer may be exposed to blood flow in the azygosvein or alternatively may be contained in a chamber in an inflatableballoon filled with coolant (e.g., circulating coolant such as sterilewater or saline). The ultrasound energy is directed toward the distalreflector balloon and reflected and focused into tissue surrounding thesplanchnic nerve. The advantage of this approach is that an activeultrasound transducer can be made larger and is not required to gothrough the sharp turn from azygos to intercostal vein. A secondadvantage is that several intercostal veins can be used to targetablation with the same catheter.

Renal Dynamics has disclosed a renal denervation device and method ofuse that deploys RF electrodes (e.g., 8 RF electrodes spaced apart inquadrants) mounted to radially expandable struts forming a basket toablate tissue around a renal artery and also includes a non-occludingmembrane intended to isolate blood, minimizing heat loss and enablingdeeper tissue ablation, for example EP2934357, WO2016132340, thedisclosures of which are incorporated by reference herein and containmany features useful for transvascular ablation of tissue. The devicerelies on blood flow in a renal artery to provide thermal propertiessuch as electrode cooling for creating ablations. Potentially in somepatients there could be sufficient blood flow in an intercostal to coolelectrodes however it would be much less than in a renal artery andalternative energy delivery parameters may compensate for the lowerblood flow. For example, a pulsed RF waveform that allows surface tissueto cool during amplitude pauses may generate an effective 5 mm deepablation. FIGS. 30A and 30B show an RF ablation catheter 260 having anelongated shaft 275 with a proximal region and a distal region, and anablation assembly 276 mounted to the distal region. The ablationassembly 276 is made of a basket of elastic struts 261 (e.g., 3 or 4rows of struts) each having at least one electrode 262 mounted to it ina configuration that allows the basket to have a contracted deliverystate having a diameter of about 1.7 mm and an expanded ablation statehaving a diameter in a range of about 2.5 mm to 4 mm. A non-occluding,radially expandable, tubular membrane 263 may be electrically insulativeand connected to (e.g., positioned over) the struts 261 with theelectrodes 262 on the outer surface of the membrane. The membrane 263may prevent electrical RF energy from shunting through the blood so itis concentrated through the vessel wall to the target ablation zone.Optionally, additional electrode cooling may be achieved throughinjecting a coolant 264 such a saline through the lumen of thenon-occluding membrane to cool electrodes with convection. Since bloodflows in the intercostal vein in a direction that is from the distal endof the device toward the azygos vein, coolant may be injected through acoolant delivery port 265 that is at the distal end of the basket so itflows in the same direction as the blood flow. The dimensions of thestruts making the basket may be modified to fit a smaller vessel, forexample having a maximum diameter in a range of 3 to 4 mm. The strutsmay comprise narrowed sections 266 between mounted electrodes (e.g., atthe same longitudinal distance) that have greater flexibility than therest of the struts to facilitate bending when delivering over a smallbend radius from the azygos vein to intercostal vein. The length 267 ofthe basket and position of the electrodes may be shortened to generatean ablation along the targeted ablation zone 58 that is in a range of 12to 20 mm long (e.g., 15 mm long). The electrodes may be arranged tocreate a circumferential ablation along the full length of the targetedablation zone. Alternatively, electrodes may be mounted only on one ortwo struts of the basket to ablate only a segment (e.g., 50%, 40%, 30%,25%) of the vessel circumference for directional ablation. A radiopaquemarker 268 that identifies radial direction of the basket may bepositioned on the catheter's distal region (e.g., on the struts, as thestruts, using the position of the electrodes which may be radiopaque, onthe catheter shaft near the basket). As shown in FIG. 30B, a crosssection of FIG. 30A, struts 261 may have a width 269 of about 0.5 mm andthickness 270 of about 0.13 mm. Electrodes 262 may have a width 271 ofabout 1 mm and a maximum thickness 272 of about 0.33 mm tapered tonarrower thickness 273 at the edges of about 0.25 mm. Electrode lengthmay be about 3 to 5 mm. Optionally, the shaft may have a flexible neck274 within 10 mm proximal of the balloon basket to allow the distalregion to sit well in the intercostal vein.

Dual Electrode Embodiments

The disclosure that follows is generally related to systems, devices,and methods for transvascular ablation of target tissue. The devices andmethods may, in some examples, be used for splanchnic nerve ablation fortreatment of heart failure. For example, the devices disclosed hereinmay be advanced endovascularly to a target vein in the region of athoracic splanchnic nerve (TSN), such as a greater splanchnic nerve(GSN) or a TSN nerve root. Any of the disclosure herein related to nerveablation may apply to the following disclosure, and is incorporated byreference into the disclosure that follows.

Dual Electrode Catheter

FIG. 31 illustrates an exemplary embodiment of an ablation device in anexemplary position for use. In FIG. 31 , device 120 is placed in anexemplary location for transvascular ablation of a target nerve (e.g.,GSN 52, GSN roots 53, TSN) from a small vein (e.g., T11 intercostal vein55, T10 intercostal vein 56, T9 intercostal vein, lower threeintercostal veins) is shown. The device 120 includes an elongate shaft121, a catheter proximal portion (not shown) intended to remain out ofthe patient in use and may be manipulated by a physician, and a catheterdistal portion 122 comprising at least two ablation elements (which mayalso be referred to herein as ablation members) including a proximalelectrode 123 and a distal electrode 124, and an occlusion element 128there between. Any of the occlusion elements herein may also be referredto as an occlusion member.

In the example shown, the catheter 120 includes a guidewire lumen (notshown) extending therethrough, and the catheter distal portion 122includes a guidewire exit port 126 positioned at or near the distal endof the distal section 122, so that the catheter 120 can be advanced intothe venous system along a guidewire 79. The catheter may be deliveredthrough a delivery sheath 80. In some examples, the elongate shaft 121can include a braided shaft to facilitate torqueability (i.e.,transmission of torque from the catheter proximal portion to thecatheter distal portion 122), particularly over a tortuous deliverypath. In alternative examples, the guidewire lumen and exit port 126 maybe omitted, and the catheter may be advanced into a patient'scardiovascular system (e.g., into a vein or artery) without the aid of aguidewire. For example, a catheter may have a deflectable distal tipcontrollable by an actuator on a handle on the proximal portion thatcontrols tension of a pull wire connected to the deflectable distal tipthat can bend (e.g., a 90 degree deflectable bend with a bend radius ina range of 6 to 15 mm) to facilitate advancement from a first vein intoa second vein or an ablation catheter may be advanced through a deliverysheath that may be advanced over a guide wire to a target vessel whereinthe guidewire may be removed before advancing the ablation catheter.

The ablation elements 123 and 124 shown in FIG. 31 comprise electrodesthat are each connected their own independent conductor that passesthrough the catheter shaft 121 to the proximal region of the catheterwhere they are connectable to an energy delivery console, which mayoperate the two electrodes in bipolar RF mode. Each electrode may havedimensions suitable to fit into a small vessel (e.g., a T10 intercostalvein 56, a T11 intercostal vein 55, a T9 intercostal vein, a human'slower three intercostal veins) and for delivering RF ablation energy.Each electrode 123 and 124 may be cooled with irrigation and optionallycomprise irrigation exit ports 129 on their sides or ends in fluidcommunication with at least one irrigation lumen (not shown) passingthough the catheter shaft 121 to the proximal region of the catheterwhere it is connectable to an irrigation fluid supply. Optionallyseparate irrigation lumens may be present to separately supplyirrigation to each electrode. Separate irrigation lumens may facilitatemore precise control of irrigation flow rate to each electrode. Theirrigation exit ports 129 may have a diameter of about 0.020″+/−0.005″.Alternatively, irrigation of the electrodes may be closed looped andcontained within the catheter instead of delivering irrigation fluidthrough exit ports into the blood stream. An embodiment with closed-loopirrigation may include at least one irrigation fluid delivery lumen thatdelivers fluid to a chamber within each electrode and at least onereturn lumen that returns the fluid to the proximal region of thecatheter. Each electrode 123 and 124 may have a length in a range of 3to 5 mm (e.g., 4 mm) and outer diameter in a range of 1.5 to 3 mm (e.g.,2 mm). The distance 127 between the electrodes may be in a range of 3 to6 mm (e.g., 4.5 mm). This combination of lengths of the electrodes anddistance between them along with suitable ablation energy profilesdisclosed herein and an occluding balloon 128 and electrode irrigationmay be suitable for creating a desired ablation size capable of coveringthe target region 58 including a length of up to 20 mm and depth of upto 5 mm. Each electrode 123 and 124 may have an associated temperaturesensor 131 (e.g., thermocouple or thermistor electrically connected toconductors passing through the catheter shaft 121 to the proximal regionof the catheter and connectable to the ablation energy console) in or onthe electrodes, which may be used to control energy delivery.Optionally, the electrodes may be made with a radiopaque material suchas platinum iridium.

The device 120 further comprises an inflatable occlusion member 128, inthis embodiment ablation balloon 128, positioned on the catheter shaftbetween the proximal electrode 123 and distal electrode 124. The balloonmay be made from a membrane (e.g., compliant, semi-compliant, ornon-compliant balloon) and made with techniques known in the medicaldevice industry for making catheter balloons. The membrane may be sealedto the shaft at the balloon's proximal and distal ends and define achamber within the membrane. A balloon inflation port 130 is positionedwithin the chamber and is in fluid communication with an inflation lumen(not shown) passing through the catheter shaft 121 to the proximalregion of the catheter where it is connectable to an inflation fluidsupply (e.g., gas or liquid delivered with a pressurizing device such asa syringe or pump). A temperature sensor 132 may be positioned in thechamber within the balloon 128, which may be used to monitor inflationfluid temperature. The balloon in its uninflated state may have adiameter in a range of 1.5 to 2 mm and in its inflated state may have adiameter in a range of 3 to 5 mm or approximately the size of the targetvessel lumen. Optionally, in use a first volume of inflation fluid maybe injected into the balloon when placed in a first vessel (e.g.,intercostal vein) to increase the balloon's diameter to occlude thefirst vessel, and a second volume of inflation fluid may be injectedwhen placed in a second vessel (e.g., azygos vein) to increase theballoon's diameter to occlude the second vessel. The balloon mayfunction to occlude blood flow which may provide a more stable ablationenvironment (e.g., thermal and electrical properties) around theelectrodes, to stop the target vessel from shrinking when heated whichmay provide a more stable ablation environment and maintain vesselpatency, or may direct ablation energy into the tissue.

The irrigation ports 129 may be positioned on the sides of theelectrodes 123 and 124. Optionally, the irrigation ports may havefeatures that allow irrigation fluid to continue to flow even if thevessel shrinks around the electrodes. FIGS. 32A and 32B are schematicillustrations of single electrodes not connected to a catheter, whichmay optionally replace either of the proximal and distal electrodes 123and 124 of FIG. 31 or any other embodiment herein. As shown in FIG. 32Aan alternative embodiment of an electrode 140 may comprise an irrigationport 141 positioned in a channel 142 that spans the length of theelectrode 140. Multiple ports and channels may be positioned around thecatheter, for example three ports and channels as shown. The electrode140 comprises a central lumen 143 for mounting to the shaft 121 over anirrigation lumen, electrical conductors for ablation energy, ortemperature sensors (not shown). FIG. 32B shown an alternativeembodiment of an electrode 146 (which may be used as any ablationelement or ablation member herein) may comprise an irrigation port 147positioned in a scallop 148 that spans only a portion of the length ofthe electrode 146. Multiple ports and scallops may be positioned aroundthe catheter, for example, six ports and channels as shown, althoughmore or fewer may be used. The electrode 146 comprises a central lumen149 for mounting to the shaft 121 over an irrigation lumen, electricalconductors for ablation energy, or temperature sensors (not shown).

An ablation energy delivery console (not shown) may be connectable tothe catheter 120 to delivery radiofrequency (RF) electrical current toone or more of the electrodes 123, 124 to create independent ablationssimultaneously or independently to create an overall large ablationspanning the target zone 58. Alternatively, smaller ablations may bemade by energizing only one of the electrodes in which case it may bedesired to deliver a nerve stimulation signal from the electrode toconfirm the target nerve is within the ablation zone of the singleelectrode. When both electrodes 123 and 124 are energized simultaneouslythey may be energized with in-phase voltages or currents and the two RFsources energizing each electrode may be floating with respect to eachother. Energy delivery parameters such as temperature set point fortemperature controlled energy delivery, or power set point for constantpower energy delivery can be set to the same values and automaticallymodified based on response due to differing blood flow rates orimpedance, in particular since the proximal electrode 123 may experiencegreater blood flow from the azygos vein nearby. For example, if thetemperature increase during energy delivery is slower for the proximalelectrode, that may be an indication of increased convective coolingprovided by blood flow. The power delivery algorithm can recognize theslow temperature increase and increase the power set point for theproximal electrode, or a higher temperature set point or duration ofenergy delivery may be used to compensate. Examples of energy deliveryparameters for a constant power mode may have a power set point in arange of 5 to 10 W (e.g., 7 to 8 W); a maximum irrigated electrodetemperature to avoid tissue charring may be in a range of 60 to 95 C(e.g., about 85 C); a maximum temperature in the balloon chamber may beless than 100 C; and a duration in a range of 60 s to 240 s.

An alternative energy delivery protocol may include a two-channelcombined monopolar-bipolar RF ablation configuration. This configurationcomprises delivering RF energy with different voltages to each electrode123 and 124 in monopolar mode communicating with a dispersive electrode.The difference in applied RF voltages creates a partial bipolar modeeffect with energy going from the higher-voltage electrode to the onewhich has lower voltage associated with it. This results in an intendedmonopolar-bipolar combo mode. It would be preferable, therefore, thatthe two sources driving the electrodes have a common ground. Thisconfiguration of energy delivery in combination with the electrode size,spacing and balloon of the catheter 120 may have an effect of generatingan ablation that spans the target ablation zone 58 and depth of 5 mm toablate a target nerve in the ablation zone. As described above theenergy delivery parameters such as temperature or power set points maybe automatically adjusted to compensate for the different thermal andelectrical environments of the proximal and distal electrodes.

Optionally, an energy delivery algorithm may monitor for pooling salinethat is starting to boil (e.g., via rapid fluctuations in impedanceand/or temperature). If boiling is detected (e.g., with a temperaturesensor), then the algorithm may reduce power and/or temporarily shut offpower and wait a predetermined time or wait until temperature dropsbelow some threshold (e.g., 95 C) then ramp up power again. Thealgorithm may identify a maximum power where boiling was previouslydetected and use that value to limit the max power during the resumedpower period. Alternately the algorithm may choose a lower temperatureset point than the target temperature that previously resulted in theboiling.

The console may also control electrode irrigation by turning anirrigation fluid pump on and off so irrigation is occurring while RF isdelivered. The flow rate of the irrigation may be set to a constant rate(e.g., about 2 mL/min). Alternatively, a greater flow rate may bedelivered to the distal electrode since it has less cooling from bloodflow than the proximal electrode when used as shown in FIG. 31 .Alternatively, flow rate may be higher to an electrode that has a highertemperature to power ratio.

Methods of using the device 121 include versatile positioning and energydelivery profiles which may be valuable for use in a range of anatomicalvariability. In particular when using the device for GSN ablation fromwithin intercostal veins a method of use may comprise ablating a firsttarget region from within a lowest intercostal vein (e.g., T11intercostal vein) followed by ablating a second target region fromwithin a second lowest intercostal vein (e.g., T10 intercostal vein). Afirst method of use may comprise fully delivering both electrodes 123and 124 into the lowest intercostal vein 55 such that the proximal end129 of the proximal electrode 123 is aligned with the ostium 59 wherethe intercostal vein connects to the azygos vein 50, performing anablation procedure, repositioning the distal region 122 to the secondlowest intercostal vein 56, and performing a second ablation procedure.

In some patients one or more target intercostal veins may be too narrowor tortuous to deliver both electrodes 123 and 124 fully into the targetvein. In this scenario a second method of use may comprise insertingonly a distal electrode 124 into the target vein and creating a shorterablation compared to the first method of use. It may or may not bepossible to deliver both electrodes into a second or third lowestintercostal vein and ablate the full target regions. Optionally, whenablating with only the distal electrode 124 in an intercostal veinablation energy may be delivered only to the distal electrode 124wherein an electrical circuit is competed by a dispersive electrodeoptionally elsewhere on the catheter or on the patient's skin.Alternatively, the proximal electrode 123 may complete the circuit in abipolar mode wherein the proximal electrode is expected to be positionedwithin the azygos vein where greater blood flow cools the proximalelectrode and vessel. The occlusion balloon 128 may be inflated todirect blood flow away from the ostium.

A third method of use may include conducting the steps of the firstmethod of use and additionally moving the device to a position as shownin FIG. 33 wherein the distal electrode 124 is in the intercostal vein55 (or other intercostal vein) and the balloon 128 is inflated to directazygos vein blood flow away from the ablation zone, and creating furtherablations around the intercostal veins and within 10 mm (e.g., 6 mm) ofthe ostium 59. Blood flow in the azygos vein 50 may cool tissue near theostium that is within the target ablation region 58 potentially impedingan efficacious ablation size.

Any of the methods of use described herein may further comprise avisualization step to determine the location of the device in the targetnerve. Medical imagining technology such as fluoroscopy may be used toimage the device, in particular radiopaque aspects of the device such asthe proximal and distal electrodes 123 and 124 in relation to thepatient's vasculature. A radiopaque contrast agent may be injected intothe patient's blood stream (e.g., via the delivery sheath 80, guidewirelumen and exit port 126, or electrode irrigation ports 129) tofacilitate fluoroscopic imaging.

Dual Electrode Catheter with Recessed Electrodes

In an alternative embodiment of a catheter 155 for transvascularablation (e.g., of a TSN or GSN from an intercostal vein) is shown inFIGS. 34A and 34B. This catheter 155 has at least one electrode fordelivering ablation energy or nerve stimulation signals. As shown thecatheter 155 has two electrodes: a proximal electrode 156 and a distalelectrode 157 separated by a distance 158. The electrodes 156 and 157are mounted to a shaft 159 of the distal region 160 of the catheter andhave a diameter 161 that is less than the diameter 162 of the shaft 159of the distal region. For example, for transvascular ablation fromwithin an intercostal vein the electrode diameter 161 may be in a rangeof 1.5 to 2.5 mm, the shaft diameter 162 may be in a range of 2 to 3 mm,and the electrode diameter 161 may be less than the shaft diameter 162by 0.2 to 1 mm. Delivering ablation energy from within a small vessel(e.g., less than 4 mm) may result in heating the vessel wall, which maycause it to shrink. By recessing the electrodes' surface from the shaftsurface the shaft 159 of the distal region 160 may hold the vessel wallaway from the electrode surface and maintain a gap, which may provide amore consistent thermal and electrical environment during energydelivery, which in turn may improve safety and efficacy of energydelivery. Each electrode 156 and 157 may be cooled with irrigation andoptionally comprise irrigation exit ports 163 on their sides in fluidcommunication with at least one irrigation lumen (not shown) passingthough the catheter shaft 159 to the proximal region of the catheterwhere it is connectable to an irrigation fluid supply. Electrodeirrigation cools the electrodes during energy delivery so they candeliver greater ablation power, which may be needed to ablate a depth ofup to 5 mm from the vessel wall (e.g., for GSN ablation). Optionallyseparate irrigation lumens may be present to separately supplyirrigation to each electrode. Separate irrigation lumens may facilitatemore precise control of irrigation flow rate to each electrode. Theirrigation exit ports 163 may have a diameter of about 0.020″+/−0.005″.Alternatively, irrigation of the electrodes may be closed-looped andcontained within the catheter instead of delivering irrigation fluidthrough exit ports into the blood stream. An embodiment with closed-loopirrigation may include at least one irrigation fluid delivery lumen thatdelivers fluid to a chamber within each electrode and at least onereturn lumen that returns the fluid to the proximal region of thecatheter. In embodiments having open-looped irrigation as shown in FIGS.34A and 34B the shaft 159 of the distal region 160 may have channels orgrooves 164 extending along at least a portion of length of the shaft159 to allow fluid to flow along the channels 164 even if the vesselshrinks around the shaft 159. This may avoid unwanted pooling orstagnant irrigation fluid around the electrodes 156 and 157 which couldcause overheating of the fluid and ineffective or unsafe ablation energydelivery. FIG. 34B shows a cross section of shaft 159 at a cross sectionlocation indicated on FIG. 34A, wherein the shaft 159 has a largerdiameter 162 than the diameter 161 of the electrode 157 and the shaft159 has channels 164 for fluid flow along the length of the shaft. Alsoshown is a guide wire lumen 326 for delivery over a guidewire 79 (shownin FIG. 34A).

Irrigation fluid may optionally be hypertonic saline, which can conductelectrical ablation energy from the electrodes 156 and 157 to the vesselwall even if the electrodes are not in contact with the wall.

Each electrode 156 and 157 may have a length in a range of 3 to 5 mm(e.g., 4 mm). The distance 158 between the electrodes may be in a rangeof 3 to 6 mm (e.g., 4.5 mm). This configuration may allow ablation oftissue within the target ablation zone 58 suitable for GSN ablation.

The electrodes (123 and 124 of the device of FIG. 31 , or 156 and 157 ofthe device of FIG. 34A) may alternatively be coiled wire electrodes madeof an elastic and electrically conductive material such as springstainless steel. Coil electrodes may improve flexibility of the distalregion of the catheters allowing them to traverse a tight bend such asthe bend from an azygos vein to intercostal vein. Coil electrodes may beirrigated by passing fluid from an irrigation lumen through small gapsin the coil pitch.

In some embodiments such as the device shown in FIG. 31 the ablationelements 123 and 124 are electrically conductive around thecircumference of the electrodes capable of delivering ablative energy tothe target region 58 of the target vessel 55 circumferentially, in otherwords in a radially symmetric pattern. A benefit of this feature may bethat a user does not need to consider radial orientation or torque thecatheter adjust radial orientation, which may reduce procedure time oruser error. However, in alternative embodiments an ablation element maydirect ablation energy toward a segment of the circumference, forexample the segment may be less than or equal to 50% of thecircumference (e.g., less than 40%, less than 30%, less than 25%). Adirectional ablation catheter may direct ablation energy toward a targetnerve, which may require less ablation energy, reduce a risk of injuringnon-target tissue, reduce pain, or reduce injury or shrinkage of thetarget vessel. When used to ablate a TSN or GSN from an intercostalvein, the TSN or GSN is always in the same direction relative to thevein, which is away from the vertebra and toward the lung. In someexamples (not shown), a radiopaque marker of the catheter may be used tofacilitate radial orientation of the catheter. The desired orientationmay be the orientation in which the directed ablation energy will beaimed in a radial direction that is away from the vertebra (e.g.,opposite the vertebra) and towards the lung. For example, if the targetvessel is a right T11 intercostal vein, a C-arm fluoroscope may becentered on a T11 vertebra, and optionally rotated from ananterior-posterior center position (AP position) to the patient's rightside to obtain an angle that is approximately orthogonal to the tangentof the vertebra. In this position, it can be desired to have thedirected ablation energy aimed in a radial direction toward the C-armhead, which is where the TSN often traverses intercostal veins. Thecatheter may be torqued to rotate the catheter distal section 122 withinthe intercostal vein until the radiopaque marker indicates that theablation energy will be aimed toward the C-arm and thus toward thetarget nerve. The radiopaque marker may be configured to distinguishwhen the radiopaque marker is rotationally aimed at a C-arm head. Sincethe position of the radiopaque marker is circumferentially aligned withthe direction of ablation, the radiopaque marker can be used to indicatewhen the direction of ablation is aimed at a C-arm head. The radiopaquemarker is made from a radiopaque material and is asymmetric in shape.For example, the radiopaque marker may be N-shaped. If the radiopaquemarker is facing towards the C-arm head, the radiopaque marker willappear as the letter N. If the radiopaque marker is facing away from theC-arm head (e.g., toward the vertebra), the radiopaque marker willappear as a backwards letter N. If the radiopaque marker is sideways inrelation to the C-arm, the radiopaque marker will appear as a line.Optionally, a device may further include an additional radiopaque markerthat is configured to visually indicate when the rotational position ofthe catheter's distal section 84 is within a set tolerance.Particularly, the additional radiopaque marker can include two lines thecenter of which is circumferentially spaced from the first radiopaquemarker by about 180 degrees, so that the first radiopaque marker appearsbetween the lines of the additional radiopaque marker when theorientation is within the set tolerance. When the orientation is outsidethe set tolerance, the radiopaque marker will overlap one of the linesof the additional radiopaque marker or will be outside of the lines ofthe additional radiopaque marker. For example, the set tolerance may beup to 45 degrees on either side of perfect alignment (e.g. up to 35degrees, or 25 degrees, or 15 degrees, or 5 degrees).

Electrodes may be configured for directional energy delivery byelectrically insulating a portion of the electrodes facing away from theablation direction.

Methods of Treatment

In some embodiments of a GSN ablation procedure herein, the lowestintercostal vein is first targeted because in a majority of patients afully formed GSN traverses the lowest intercostal vein within the targetregion that is between the adjoining azygos vein and to a distance up to20 mm into the intercostal vein from the ostium. However, in somepatients where a first ablation is not sufficient, a test may be done toassess a clinical effect and subsequent ablations of target regions atone or two additional levels may be done to achieve a clinicallysignificant effect. For example, the following description is anexemplary method of treating heart failure in a human patient byablating a thoracic splanchnic nerve. A distal region of an ablationcatheter comprising an ablation element can be delivered to a firstintercostal vein (e.g., the lowest intercostal vein, a T11 intercostalvein) of the patient. Ablation energy can then be delivered from theablation catheter to create a first lesion (e.g., a lesion having alength in a range of 10 to 20 mm, e.g., in a range of 12 to 15 mm) intissue up to 5 mm from the first intercostal vein. The distal region ofthe ablation catheter can be moved to a second intercostal vein that issuperior to (e.g., superior to and adjacent to) the first intercostalvein. An ablation confirmation test can then be performed. Monitoringcan be performed for a physiological response (e.g., splanchnicvasoconstriction, increased heart rate, increased blood pressure) to theablation confirmation test. If the physiological response demonstratesthat the first lesion did not provide a clinically significant amount ofGSN blocking (e.g., by observing a lack of physiological response) thenablation energy can be delivered from the ablation catheter to create asecond lesion in tissue up to 5 mm from the second intercostal vein. Thedistal region of the ablation catheter can be moved to a thirdintercostal vein that is superior to (e.g., superior and adjacent to)the second intercostal vein. The same or different ablation confirmationtest can be performed, followed by another monitoring test. If thephysiological response demonstrates that the first lesion and secondlesion did not provide a clinically significant amount of GSN blocking(e.g., by observing a lack of physiological response) then ablationenergy can be delivered from the ablation catheter to create a thirdlesion in tissue up to 5 mm from the third intercostal vein. Any of theablation confirmation tests may comprise delivering a nerve stimulationsignal from a stimulation electrode positioned on the distal region ofthe ablation catheter configured to generate an action potential in thethoracic splanchnic nerve. Alternatively or in addition to, the ablationconfirmation test may comprise a leg raise test. Alternatively or inaddition to, the ablation confirmation test may comprise adding fluidvolume to the venous system. Alternatively or in addition to, theablation confirmation test may comprise a hand-grip test.

In exemplary methods in which an ablation confirmation test includes aleg raise test, the method may comprise any of the following steps.Prior to ablation in the lowest intercostal vein, a baseline measurementmay be obtained by raising the legs and measuring the change in centralvenous pressure and waiting for equilibration, that is a measure of thetotal venous compliance including the central veins and splanchnic bed.The legs can then be lowered, to allow equilibration so bloodredistributes back to the legs. An ablation in the lowest intercostalvein (e.g. T11) can then be performed as set forth herein. The legs canthen be raised, followed by waiting for equilibration and re-measurecentral venous pressure. A measurement can then be made to determine ifthere was an appropriate reduction in total venous compliance. If yes,then the GSN has successfully been ablated. If no, then an ablation inthe next higher intercostal vein (e.g., T10) can be performed, as setforth herein. The measurement can be repeated. A determination can thenbe made to see if there was an appropriate reduction in total venouscompliance. If yes, then the GSN has successfully been ablated. If no,then an ablation in the next higher intercostal vein (e.g., T9) can beperformed.

In exemplary methods in which an ablation confirmation test comprises ahand-grip or other activity that increases sympathetic nervous system(SNS) outflow to the splanchnic bed may comprise the following steps. Anablation can be performed in a lowest intercostal vein (e.g., T11).Venous compliance can then be measured. A hand-grip can then beperformed for a predetermined amount of time (e.g., 60 seconds). Venouscompliance can then be remeasured. If there is no change in venouscompliance, the initial ablation was sufficient to achieve a clinicallysignificant outcome. If there still is a decrease in compliance, some ofthe SNS activity caused by the hand-grip is getting through. Theablation in the lowest intercostal vein was thus insufficient to achievea clinically significant effect. An ablation in the next higherintercostal vein (e.g., T10) can then be performed. A hand grip test fora predetermined amount of time (e.g., 60 seconds) can be performed.Venous compliance can then be remeasured. If there is no change incompliance, the second ablation was sufficient. If there is a decreasein compliance, some of the SNS activity caused by the hand-grip isgetting through, and the ablation in the next higher intercostal veinwas thus insufficient to achieve a clinically significant effect.Ablation is the next higher intercostal vein (T9) can then be performed.The procedure is done at this point as ablation at a level higher thanthe 3rd lowest intercostal vein is not anticipated.

An ablation confirmation test may include delivering a nerve stimulationsignal and monitoring and assessing a physiological response. Any of themethods of use described herein may further comprise a nerve stimulationstep. For example, the electrodes used for ablation or other electrodesmay be used to deliver one or more nerve stimulation signals. Forexample, the proximal and distal electrodes (123 and 124 of FIGS. 31 and33 , or 156 and 157 of FIG. 34A) may be used to deliver one or morenerve stimulation signals. Each electrode is electrically connected viaindependent conductors (not shown) travelling through the catheter tothe proximal end of the catheter where they are connectable to a nervestimulation signal supply, which may also be a computer controlled RFablation energy console. The console may switch between delivering astimulation signal and ablation signals so the electrodes may be usedfor either stimulation or ablation. In use the electrodes (e.g., 123 and124 of FIG. 31 ) may be positioned at a proximal and distal end of atarget region 58 of a target vessel 55, which can be visualized forexample with fluoroscopy by placing the proximal electrode (e.g., 123 ofFIG. 31 ) at the ostium 59 of the target vessel 55 as shown in FIG. 31or FIG. 34A for example. The nerve stimulation electrodes may deliver anerve stimulation signal in bipolar mode concentrating the signalbetween the two electrodes to generate an action potential of a nervepositioned between them and also within a predicted ablation zone. Thedistance between the two nerve stimulation electrodes of no more than 25mm (e.g., 4 to 6 mm) ensures a pacing vector having a nerve stimulationsignal strength capable of stimulating a nerve within the vector. Nervestimulation (i.e., pacing) parameters may include 50 Hz and 1V used togenerate an action potential of a TSN or GSN. Stimulation of a TSN orGSN may result in a measurable physiological response for example anepigastric response such as contraction of the rectus abdominis muscle,increased heart rate, or increased blood pressure. A positivestimulation of a TSN or GSN can confirm the ablation element is in anappropriate location to ablate the targeted TSN or GSN while lack ofresponse can suggest the ablation element needs to be moved. Nervestimulation parameters may include 2 Hz and 2V used to stimulateintercostal nerves or the sympathetic trunk to confirm clearance fromintercostal nerves when a lack of intercostal muscle response ismeasured or to confirm clearance from the sympathetic trunk when a lackof response from sympathetic trunk is measured. The electrodes mayoptionally or alternatively be used to measure bioimpedance and phase oftissue in the pacing range which can be used to detect presence of nervetissue, detect tissue changes caused by ablation, detect abruptimpedance changes which may be predictive of ensuing safety concerns(e.g., blood coagulation, overheating, bubble formation). Optionally, anerve stimulation signal may have features that reduce or eliminatestimulation of pain fibers and yet stimulate a target TSN or GSN.

In any of the methods herein, including ablation confirmation testsherein, not all of the steps need necessarily to be performed. And someof the steps may occur in different orders. It is of note that theprocedures herein are intending to target particular nerves or nerveroots, and are doing so from particular target veins, and even withinthose veins are placing ablation elements or members within certainregions. The anatomical regions that are being accessed and targetednecessitate certain design requirements. In other treatments that aretargeting different anatomical locations for placement, and targetingdifferent target nerves, the device design constraints for thoseapproaches are very different, and thus the devices that can be used inthose treatments may be very different. The disclosure herein thusprovides specific reasons for designing particular devices, and thosereasons include being able to effectively carry out the treatmentsspecifically set forth herein.

While the above description provides examples of one or more processesor apparatuses, it will be appreciated that other processes orapparatuses may be within the scope of the accompanying claims.

Even if not specifically indicated, one or more techniques described inthis disclosure may be implemented, at least in part, in hardware,software, firmware or any combination thereof. For example, variousaspects of or more techniques or components may be implemented withinone or more processors, including one or more microprocessors, digitalsignal processors (DSPs), application specific integrated circuits(ASICs), field programmable gate arrays (FPGAs), programmable logiccircuitry, or the like, either alone or in any suitable combination. Theterm “processor” or “processing circuitry” may generally refer to any ofthe foregoing circuitry, alone or in combination with other circuitry,or any other equivalent circuitry.

Such hardware, software, or firmware may be implemented within the samedevice or within separate devices to support relevant various operationsand functions described in this disclosure. In addition, any of thedescribed units, modules or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

When implemented in software, the functionality ascribed to systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as random access memory(RAM), read only memory (ROM), non-volatile RAM (NVRAM), electricallyerasable programmable ROM (EEPROM), Flash memory, and the like. Theinstructions may be executed by a processor to support one or moreaspects of the functionality described in this disclosure.

To the extent any amendments, characterizations, or other assertionspreviously made (in this or in any related patent applications orpatents, including any parent, sibling, or child) with respect to anyart, prior or otherwise, could be construed as a disclaimer of anysubject matter supported by the present disclosure of this application,Applicant hereby rescinds and retracts such disclaimer. Applicant alsorespectfully submits that any prior art previously considered in anyrelated patent applications or patents, including any parent, sibling,or child, may need to be re-visited.

Specific embodiments described herein are not intended to limit anyclaim and any claim may cover processes or apparatuses that differ fromthose described below, unless specifically indicated otherwise. Theclaims are not limited to apparatuses or processes having all of thefeatures of any one apparatus or process described below or to featurescommon to multiple or all of the apparatuses described below, unlessspecifically indicated otherwise. It is possible that an apparatus orprocess described below is not an embodiment of any exclusive rightgranted by issuance of this patent application. Any subject matterdescribed below and for which an exclusive right is not granted byissuance of this patent application may be the subject matter of anotherprotective instrument, for example, a continuing patent application, andthe applicants, inventors or owners do not intend to abandon, disclaimor dedicate to the public any such subject matter by its disclosure inthis document.

What is claimed is:
 1. A vascular catheter, comprising: a catheter shaftcomprising an exit port and a needle assembly lumen; a telescopic needleassembly, the telescopic needle assembly configurable from a firstposition to a second position, wherein the telescopic needle assembly iswithin the catheter in the first position and in the second positionextends from the exit port, the needle assembly configured to puncturevascular tissue when transitioned to the second position, the needleassembly comprising: a first section and a second section, the firstsection surrounding the second section, and wherein the second sectioncomprises an outer surface with one or more electrodes thereon, whereinin the second position, the first section extends outward from theneedle assembly lumen and the second section extends outwards from thefirst section, and wherein the first and second sections exit the exitport in a straight direction when transitioning to the second position;and a guidewire lumen.
 2. The vascular catheter of claim 1, wherein theneedle assembly comprises a third section that is a telescopingrelationship with the first and second sections.
 3. The vascularcatheter of claim 1, wherein the needle assembly comprises a thirdsection that is co-axial with the first and second sections.
 4. Thevascular catheter of claim 1, wherein the one or more electrodescomprise first and second electrodes positioned and adapted to beoperated in bipolar mode.
 5. The vascular catheter of claim 1, furthercomprising a marker configured to indicate radial orientation.
 6. Thevascular catheter of claim 1, further comprising a stimulation electrodefor delivering a nerve stimulation signal.
 7. The vascular catheter ofclaim 1, wherein first section has a sharped distal end.
 8. The vascularcatheter of claim 1, further comprising a base electrode on an outersurface of the catheter.
 9. The vascular catheter of claim 1, whereinthe one or more electrodes comprises a first and a second electrode, andwherein the vascular catheter is configured to provide a first ablationenergy to the first electrode and a second ablation energy to the secondelectrode, wherein the first ablation energy and the second ablationenergy are independent of one another.
 10. The vascular catheter ofclaim 1, further comprising an electrode advancer configured to extendthe needle assembly and one or more electrodes through the exit port.11. A vascular catheter, comprising: a catheter shaft comprising an exitport and a needle assembly lumen; a telescopic needle assemblyconfigurable from a first position to a second position, wherein thetelescopic needle assembly is within the catheter in the first positionand in the second portion extends from the exit port, the needleassembly comprising: a first section and a second section, the firstsection surrounding the second section, the second section having adistal end configured to puncture vascular tissue, and one or moreelectrodes, wherein in the second position, the first section extendsoutwards from the needle assembly lumen, the second section extendsoutwards from the first section, and the first and second sections havestraight configurations; and a guidewire lumen.
 12. The vascularcatheter of claim 11, wherein the needle assembly comprises a thirdsection that is a telescoping relationship with the first and secondsections, wherein the second section surrounds the third section and thethird section extends outward from the second section.
 13. The vascularcatheter of claim 11, wherein the needle assembly comprises a thirdsection within the second section that is co-axial with the first andsecond sections.
 14. The vascular catheter of claim 11, wherein the oneor more electrodes comprises first and second electrodes positioned andadapted to be operated in bipolar mode.
 15. The vascular catheter ofclaim 11, further comprising a marker configured to indicate radialorientation.
 16. The vascular catheter of claim 11, further comprising astimulation electrode for delivering a nerve stimulation signal.
 17. Thevascular catheter of claim 11, further comprising a base electrode on anouter surface of the catheter.
 18. The vascular catheter of claim 11,wherein the one or more electrodes comprises a first and a secondelectrode, and wherein the vascular catheter is configured to provide afirst ablation energy to the first electrode and a second ablationenergy to the second electrode, wherein the first ablation energy andthe second ablation energy are independent of one another.
 19. Thevascular catheter of claim 11, further comprising an electrode advancerconfigured to extend the needle assembly and the one or more electrodesthrough the exit port.